The chemokine CXCL13 in acute neuroborreliosis

Objective Recent studies have suggested an important role of the B cell chemoattractant CXCL13 in acute neuroborreliosis (NB). Our aim was to confirm the diagnostic role of CXCL13 and to evaluate its relevance as a therapy response and disease activity marker in NB. Methods CXCL13 was measured in cerebrospinal fluid (CSF) and serum of patients with NB (n = 28), systemic borreliosis (SB, n = 9), Guillaine-Barre syndrome (GBS, n = 11), Bell's palsy (BP, n = 19), other cranial nerve palsies (CNP, n = 5), cephalgia (C, n = 20), bacterial CNS infections (B-CNS-I, n = 16) and viral CNS infections (V-CNS-I, n = 18). For follow-up studies, serial sample pairs were evaluated from 25 patients with NB (n = 56), 11 with B-CNS-I (n = 25) and 14 with V-CNS-I (n = 36). Results CSF-CXCL13 was significantly elevated in NB compared with other neurological diseases (p<0.001). Using receiver operating characteristic analysis, 337 ng/g was determined as a cut-off with a sensitivity of 96.4% and a specificity of 96.9%. Of all the parameters investigated, CSF CXCL13 showed the fastest response to antibiotic therapy, decreasing significantly (p = 0.008) within 1 week. In untreated patients, CSF CXCL13 was elevated in patients with a short duration of disease. Borrelia burgdorferi antibody index showed no significant (p = 0.356) change over follow-up. Conclusions The study confirms the relevance of CXCL13 as a diagnostic biomarker of NB and suggests that CSF CXCL13 in NB is linked to duration of disease and could be a marker of disease activity and response to antibiotic therapy

Grossansätze zur Herstellung von α,α,α',α'-Tetraaryl-1,3-dioxolan-4,5-dimethanolen (TADDOLe): Nützliche Hilfsstoffe für die EPC-Synthese und ihre Struktur im Festkörper

The large-scale preparation of α,α,α',α'-tetraaryl-1,3-dioxolan-4,5-dimethanol derivatives is described. It consists of acetalization of dimethyl tartrate and Grignard addition. The diols 2–12 thus obtained are crystalline and stable. They are useful as versatile auxiliaries for enantioselective reactions and for resolutions by clathrate formation. The X-ray crystal structure of the inclusion compound from one of the TADDOLs and CCl4 is described (6·2 CCl4) and compared with the structures of analogous derivatives, including C2-symmetrical diphosphines. Reference is given to other chiral auxiliaries containing the diaryl-methanol group

Not a Second Time? John Lennon’s Aeolian Cadence Reconsidered

In 1963 William Mann coined the term “aeolian cadence” to describe a harmonic progression in the song “Not a Second Time” by the Beatles. This term has caused confusion ever since. In this article, I discuss why Mann might have used this confusing phrase and how it relates to this song by John Lennon. I will argue that, in the debate that ensued from Mann’s observations, his commentators were primarily preoccupied with terminology and definitions but forgot to listen to Lennon. More specifically, I argue that, if the interplay between the music and lyrics is considered, the famous cadence in “Not a Second Time” can best be interpreted as “deceptive.

Defining optimal soybean seeding rates and associated risk across North America

Soybean [Glycine max (L.) Merr.] seeding rate research across North America is typically conducted in small geo-political regions where environmental effects on the seeding rate × yield relationship are minimized. Data from 211 individual field studies (∼21,000 data points, 2007–2017) were combined from across North America ranging in yield from 1,000– 7,500 kg ha−1. Cluster analysis was used to stratify each individual field study into similar environmental (soil × climate) clusters and into high (HYL), medium (MYL), and low (LYL) yield levels. Agronomically optimal seeding rates (AOSR) were calculated and Monte Carlo risk analysis was implemented. Within the two northern most clusters the AOSR was higher in the LYL followed by the MYL and then HYL. Within the farthest south cluster, a relatively small (±15,000 seeds ha−1) change in seeding rate from the MYL was required to reach the AOSR of the LYL and HYL, respectively. The increase in seeding rate to reach the LYL AOSR was relatively greater (5x) than the decrease to reach the HYL AOSR within the northern most cluster. Regardless, seeding rates below the AOSR presented substantial risk and potential yield loss, while seeding rates above provided slight risk reduction and yield increases. Specific to LYLs and MYLs, establishing and maintaining an adequate plant stand until harvest maximized yield regardless of the seeding rate, while maximizing seed number was important with lower seeding rates. These findings will help growers manage their soybean seed investment by adjusting seeding rates based upon the productivity of the environment.Fil: Gaspar, Adam P.. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Mourtzinis, Spyridon. University of Wisconsin; Estados UnidosFil: Kyle, Don. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Galdi, Eric. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Lindsey, Laura E.. Ohio State University; Estados UnidosFil: Hamman, William P.. Ohio State University; Estados UnidosFil: Matcham, Emma G. University of Wisconsin; Estados UnidosFil: Kandel, Hans J.. North Dakota State University; Estados UnidosFil: Schmitz, Peder. North Dakota State University; Estados UnidosFil: Stanley, Jordan D.. North Dakota State University; Estados UnidosFil: Schmidt, John P.. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Mueller, Daren S.. University of Iowa; Estados UnidosFil: Nafziger, Emerson D.. University of Illinois; Estados UnidosFil: Ross, Jeremy. University of Arkansas for Medical Sciences; Estados UnidosFil: Carter, Paul R.. Dow Agrosciences Argentina Sociedad de Responsabilidad Limitada.; ArgentinaFil: Varenhorst, Adam J.. University of South Dakota; Estados UnidosFil: Wise, Kiersten A.. University of Kentucky; Estados UnidosFil: Ciampitti, Ignacio Antonio. Kansas State University; Estados UnidosFil: Carciochi, Walter Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina. Kansas State University; Estados UnidosFil: Chilvers, Martin I.. Michigan State University; Estados UnidosFil: Hauswedell, Brady. University of South Dakota; Estados UnidosFil: Tenuta, Albert U.. University of Guelph; CanadáFil: Conley, Shawn P.. University of Wisconsin; Estados Unido

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or

NOX2, p22phox and p47phox are targeted to the nuclear pore complex in ischemic cardiomyocytes colocalizing with local reactive oxygen species.

BACKGROUND: NADPH oxidases play an essential role in reactive oxygen species (ROS)-based signaling in the heart. Previously, we have demonstrated that (peri)nuclear expression of the catalytic NADPH oxidase subunit NOX2 in stressed cardiomyocytes, e.g. under ischemia or high concentrations of homocysteine, is an important step in the induction of apoptosis in these cells. Here this ischemia-induced nuclear targeting and activation of NOX2 was specified in cardiomyocytes. METHODS: The effect of ischemia, mimicked by metabolic inhibition, on nuclear localization of NOX2 and the NADPH oxidase subunits p22(phox) and p47(phox), was analyzed in rat neonatal cardiomyoblasts (H9c2 cells) using Western blot, immuno-electron microscopy and digital-imaging microscopy. RESULTS: NOX2 expression significantly increased in nuclear fractions of ischemic H9c2 cells. In addition, in these cells NOX2 was found to colocalize in the nuclear envelope with nuclear pore complexes, p22(phox), p47(phox) and nitrotyrosine residues, a marker for the generation of ROS. Inhibition of NADPH oxidase activity, with apocynin and DPI, significantly reduced (peri)nuclear expression of nitrotyrosine. CONCLUSION: We for the first time show that NOX2, p22(phox) and p47(phox) are targeted to and produce ROS at the nuclear pore complex in ischemic cardiomyocytes

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin