The relative stabilities of the reverse and normal polarity states of the earth's magnetic field

Recent analyses of the geomagnetic reversal sequence have led to different conclusions regarding the important question of whether there is a discernible difference between the properties of the two polarity states. The main differences between the two most recent studies are the statistical analyses and the possibility of an additional 57 reversal events in the Cenozoic. These additional events occur predominantly during reverse polarity time, but it is unlikely that all of them represent true reversal events. Nevertheless the question of the relative stabilities of the polarity states is examined in detail, both for the case when all 57 "events" are included in the reversal chronology and when they are all excluded. It is found that there is not a discernible difference between the stabilities of the two polarity states in either case. Inclusion of these short events does, however, change the structure of the non-stationarity in reversal rate, but still allows a smooth non-stationarity. Only 7 of the 57 short events are pre-38 Ma, but the evidence suggests that this is a real geomagnetic phenomenon rather than degradation of the magnetic recording or a bias in observation. This could be tested by detailed magnetostratigraphic and oceanic magnetic surveys of the Paleogene and Late Cretaceous. Overall it would appear that the present geomagnetic polarity timescale for 0–160 Ma is probably a very good representation of the actual history, and that different timescales and additional events now represent only changes in detail

Na+/K+-ATPase α1 Identified as an Abundant Protein in the Blood-Labyrinth Barrier That Plays an Essential Role in the Barrier Integrity

BACKGROUND:The endothelial-blood/tissue barrier is critical for maintaining tissue homeostasis. The ear harbors a unique endothelial-blood/tissue barrier which we term "blood-labyrinth-barrier". This barrier is critical for maintaining inner ear homeostasis. Disruption of the blood-labyrinth-barrier is closely associated with a number of hearing disorders. Many proteins of the blood-brain-barrier and blood-retinal-barrier have been identified, leading to significant advances in understanding their tissue specific functions. In contrast, capillaries in the ear are small in volume and anatomically complex. This presents a challenge for protein analysis studies, which has resulted in limited knowledge of the molecular and functional components of the blood-labyrinth-barrier. In this study, we developed a novel method for isolation of the stria vascularis capillary from CBA/CaJ mouse cochlea and provided the first database of protein components in the blood-labyrinth barrier as well as evidence that the interaction of Na(+)/K(+)-ATPase α1 (ATP1A1) with protein kinase C eta (PKCη) and occludin is one of the mechanisms of loud sound-induced vascular permeability increase. METHODOLOGY/PRINCIPAL FINDINGS:Using a mass-spectrometry, shotgun-proteomics approach combined with a novel "sandwich-dissociation" method, more than 600 proteins from isolated stria vascularis capillaries were identified from adult CBA/CaJ mouse cochlea. The ion transporter ATP1A1 was the most abundant protein in the blood-labyrinth barrier. Pharmacological inhibition of ATP1A1 activity resulted in hyperphosphorylation of tight junction proteins such as occludin which increased the blood-labyrinth-barrier permeability. PKCη directly interacted with ATP1A1 and was an essential mediator of ATP1A1-initiated occludin phosphorylation. Moreover, this identified signaling pathway was involved in the breakdown of the blood-labyrinth-barrier resulting from loud sound trauma. CONCLUSIONS/SIGNIFICANCE:The results presented here provide a novel method for capillary isolation from the inner ear and the first database on protein components in the blood-labyrinth-barrier. Additionally, we found that ATP1A1 interaction with PKCη and occludin was involved in the integrity of the blood-labyrinth-barrier

A Differential Role for Macropinocytosis in Mediating Entry of the Two Forms of Vaccinia Virus into Dendritic Cells

Vaccinia virus (VACV) is being developed as a recombinant viral vaccine vector for several key pathogens. Dendritic cells (DCs) are specialised antigen presenting cells that are crucial for the initiation of primary immune responses; however, the mechanisms of uptake of VACV by these cells are unclear. Therefore we examined the binding and entry of both the intracellular mature virus (MV) and extracellular enveloped virus (EV) forms of VACV into vesicular compartments of monocyte-derived DCs. Using a panel of inhibitors, flow cytometry and confocal microscopy we have shown that neither MV nor EV binds to the highly expressed C-type lectin receptors on DCs that are responsible for capturing many other viruses. We also found that both forms of VACV enter DCs via a clathrin-, caveolin-, flotillin- and dynamin-independent pathway that is dependent on actin, intracellular calcium and host-cell cholesterol. Both MV and EV entry were inhibited by the macropinocytosis inhibitors rottlerin and dimethyl amiloride and depended on phosphotidylinositol-3-kinase (PI(3)K), and both colocalised with dextran but not transferrin. VACV was not delivered to the classical endolysosomal pathway, failing to colocalise with EEA1 or Lamp2. Finally, expression of early viral genes was not affected by bafilomycin A, indicating that the virus does not depend on low pH to deliver cores to the cytoplasm. From these collective results we conclude that VACV enters DCs via macropinocytosis. However, MV was consistently less sensitive to inhibition and is likely to utilise at least one other entry pathway. Definition and future manipulation of these pathways may assist in enhancing the activity of recombinant vaccinia vectors through effects on antigen presentation

Probing atmospheric electric fields in thunderstorms through radio emission from cosmic-ray-induced air showers

We present measurements of radio emission from cosmic ray air showers that took place during thunderstorms. The intensity and polarization patterns of these air showers are radically different from those measured during fair-weather conditions. With the use of a simple two-layer model for the atmospheric electric field, these patterns can be well reproduced by state-of-the-art simulation codes. This in turn provides a novel way to study atmospheric electric fields

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Paleomagnetism: continents and oceans

Paleomagnetism is the study of the fossil magnetism in rocks. It has been paramount in determining that the continents have drifted over the surface of the Earth throughout geological time. The fossil magnetism preserved in the ocean floor has demonstrated how continental drift takes place through the process of sea-floor spreading. The methods and techniques used in paleomagnetic studies of continental rocks and of the ocean floor are described and then applied to determining horizontal movements of the Earth''s crust over geological time. An up-to-date review of global paleomagnetic data enables 1000 millionyears of Earth history to be summarized in terms of the drift of the major crustal blocks over the surface of the Earth. The first edition of McElhinny''s book was heralded as a "classic and definitive text." It thoroughly discussed the theory of geomagnetism, the geologicreversals of the Earth''s magnetic field, and the shifting of magnetic poles. In the 25 years since the highly successful first edition of Palaeomagnetism and Plate Tectonics (Cambridge, 1973) the many advances in the concepts, methodology, and insights into paleomagnetism warrant this new treatment. This completely updated and revised edition of Paleomagnetism: Continents and Oceans will be a welcome resource for a broad audience of earth scientists as well as laypeople curious about magnetism, paleogeography, geology, and plate tectonics.Because the book is intended for a wide audience of geologists, geophysicists, and oceanographers, it balances the mathematical and descriptive aspects of each topic.* Details the theory and methodology of rock magnetism, with particular emphasis on intrepreting crustal movements from continental and oceanic measurements* Outlines Earth history for the past 1000 million years, from the Rodinia super-continent through its breakup and the formation of Gondwana to the formation and breakup of Pangea and the amalgamation of Eurasia* Provides a comprehensive treatment of oceanic paleomagnetism* Provides a set of color pateogeographic maps covering the past 250 million years* Written by two internationally recognized experts in the fiel

CCDC 778252: Experimental Crystal Structure Determination

Related Article: W.G.Shuler, E.A.Smith, S.M.Hess, T.M.C.McFadden, C.R.Metz, D.G.VanDerveer, W.T.Pennington, P.J.Mabe, S.L.Knick, C.F.Beam|2012|J.Chem.Cryst.|42|952|doi:10.1007/s10870-012-0342-5,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 882827: Experimental Crystal Structure Determination

Related Article: W.G.Shuler, E.A.Smith, S.M.Hess, T.M.C.McFadden, C.R.Metz, D.G.VanDerveer, W.T.Pennington, P.J.Mabe, S.L.Knick, C.F.Beam|2012|J.Chem.Cryst.|42|952|doi:10.1007/s10870-012-0342-5,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 828909: Experimental Crystal Structure Determination

Related Article: W.G.Shuler, E.A.Smith, S.M.Hess, T.M.C.McFadden, C.R.Metz, D.G.VanDerveer, W.T.Pennington, P.J.Mabe, S.L.Knick, C.F.Beam|2012|J.Chem.Cryst.|42|952|doi:10.1007/s10870-012-0342-5,An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures