Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction

Signaling changes that occur in the striatum following the loss of dopamine neurons in the Parkinson disease (PD) are poorly understood. While increases in the activity of kinases and decreases in the activity of phosphatases have been observed, the specific consequences of these changes are less well understood. Phosphatases, such as protein phosphatase 1 (PP1), are highly promiscuous and obtain substrate selectivity via targeting proteins. Spinophilin is the major PP1-targeting protein enriched in the postsynaptic density of striatal dendritic spines. Spinophilin association with PP1 is increased concurrent with decreases in PP1 activity in an animal model of PD. Using proteomic-based approaches, we observed dopamine depletion-induced decreases in spinophilin binding to multiple protein classes in the striatum. Specifically, there was a decrease in the association of spinophilin with neurofilament medium (NF-M) in dopamine-depleted striatum. Using a heterologous cell line, we determined that spinophilin binding to NF-M required overexpression of the catalytic subunit of protein kinase A and was decreased by cyclin-dependent protein kinase 5. Functionally, we demonstrate that spinophilin can decrease NF-M phosphorylation. Our data determine mechanisms that regulate, and putative consequences of, pathological changes in the association of spinophilin with NF-M that are observed in animal models of PD

A boron-coated CCD camera for direct detection of Ultracold Neutrons (UCN)

A new boron-coated CCD camera is described for direct detection of ultracold neutrons (UCN) through the capture reactions $^{10}$B (n,$\alpha$0$\gamma$)$^7$Li (6%) and $^{10}$B(n,$\alpha$1$\gamma$)$^7$Li (94%). The experiments, which extend earlier works using a boron-coated ZnS:Ag scintillator, are based on direct detections of the neutron-capture byproducts in silicon. The high position resolution, energy resolution and particle ID performance of a scientific CCD allows for observation and identification of all the byproducts $\alpha$, $^7$Li and $\gamma$ (electron recoils). A signal-to-noise improvement on the order of 10$^4$ over the indirect method has been achieved. Sub-pixel position resolution of a few microns is demonstrated. The technology can also be used to build UCN detectors with an area on the order of 1 m$^2$. The combination of micrometer scale spatial resolution, few electrons ionization thresholds and large area paves the way to new research avenues including quantum physics of UCN and high-resolution neutron imaging and spectroscopy.Comment: 10 pages, 8 figure

New result for the neutron β\beta-asymmetry parameter A0A_0 from UCNA

The neutron $\beta$-decay asymmetry parameter $A_0$ defines the correlation between the spin of the neutron and the momentum of the emitted electron, which determines $\lambda=\frac{g_{A}}{g_{V}}$, the ratio of the axial-vector to vector weak coupling constants. The UCNA Experiment, located at the Ultracold Neutron facility at the Los Alamos Neutron Science Center, is the first to measure such a correlation coefficient using ultracold neutrons (UCN). Following improvements to the systematic uncertainties and increased statistics, we report the new result $A_0 = -0.12054(44)_{\mathrm{stat}}(68)_{\mathrm{syst}}$ which yields $\lambda\equiv \frac{g_{A}}{g_{V}}=-1.2783(22)$. Combination with the previous UCNA result and accounting for correlated systematic uncertainties produces $A_0=-0.12015(34)_{\mathrm{stat}}(63)_{\mathrm{syst}}$ and $\lambda\equiv \frac{g_{A}}{g_{V}}=-1.2772(20)$.Comment: 9 pages, 7 figures, updated to as-published versio

Search for neutron dark decay: n → χ + e⁺e⁻

In January, 2018, Fornal and Grinstein proposed that a previously unobserved neutron decay branch to a dark matter particle (χ) could account for the discrepancy in the neutron lifetime observed in two different types of experiments. One of the possible final states discussed includes a single χ along with an e⁺e⁻ pair. We use data from the UCNA (Ultracold Neutron Asymmetry) experiment to set limits on this decay channel. Coincident electron-like events are detected with ∼ 4π acceptance using a pair of detectors that observe a volume of stored Ultracold Neutrons (UCNs). We use the timing information of coincidence events to select candidate dark sector particle decays by applying a timing calibration and selecting events within a physically-forbidden timing region for conventional n → p + e⁻ + ν̅_e decays. The summed kinetic energy (E_(e⁺e⁻)) from such events is reconstructed and used to set limits, as a function of the χ mass, on the branching fraction for this decay channel

A new species of Eclipta Bates, 1873 from Brazil (Coleoptera, Cerambycidae) in honor of the late Ubirajara Ribeiro Martins de Souza

A new species of Eclipta Bates, 1873 from Brazil (São Paulo), E. birai, is described and illustrated. A tribute to the late Ubirajara Ribeiro Martins de Souza is provided

Protocol for the saMS trial (supportive adjustment for multiple sclerosis): a randomized controlled trial comparing cognitive behavioral therapy to supportive listening for adjustment to multiple sclerosis

BackgroundMultiple Sclerosis (MS) is an incurable, chronic, potentially progressive and unpredictable disease of the central nervous system. The disease produces a range of unpleasant and debilitating symptoms, which can have a profound impact including disrupting activities of daily living, employment, income, relationships, social and leisure activities, and life goals. Adjusting to the illness is therefore particularly challenging. This trial tests the effectiveness of a cognitive behavioural intervention compared to supportive listening to assist adjustment in the early stages of MS.MethodsThis is a two arm randomized multi-centre parallel group controlled trial. 122 consenting participants who meet eligibility criteria will be randomly allocated to receive either Cognitive Behavioral Therapy or Supportive Listening. Eight one hour sessions of therapy (delivered over a period of 10 weeks) will be delivered by general nurses trained in both treatments. Self-report questionnaire data will be collected at baseline (0 weeks), mid-therapy (week 5 of therapy), post-therapy (15 weeks) and at six months (26 weeks) and twelve months (52 weeks) follow-up. Primary outcomes are distress and MS-related social and role impairment at twelve month follow-up. Analysis will also consider predictors and mechanisms of change during therapy. In-depth interviews to examine participants’ experiences of the interventions will be conducted with a purposively sampled sub-set of the trial participants. An economic analysis will also take place. DiscussionThis trial is distinctive in its aims in that it aids adjustment to MS in a broad sense. It is not a treatment specifically for depression. Use of nurses as therapists makes the interventions potentially viable in terms of being rolled out in the NHS. The trial benefits from incorporating patient input in the development and evaluation stages. The trial will provide important information about the efficacy, cost-effectiveness and acceptability of the interventions as well as mechanisms of psychosocial adjustment.Trial registrationCurrent Controlled Trials ISRCTN91377356<br/

Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin

Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma

Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. © 2010 Macmillan Publishers Limited.Published versio

Final results for the neutron β-asymmetry parameter A₀ from the UCNA experiment

The UCNA experiment was designed to measure the neutron β-asymmetry parameter A0 using polarized ultracold neutrons (UCN). UCN produced via downscattering in solid deuterium were polarized via transport through a 7 T magnetic field, and then directed to a 1 T solenoidal electron spectrometer, where the decay electrons were detected in electron detector packages located on the two ends of the spectrometer. A value for A0 was then extracted from the asymmetry in the numbers of counts in the two detector packages. We summarize all of the results from the UCNA experiment, obtained during run periods in 2007, 2008–2009, 2010, and 2011–2013, which ultimately culminated in a 0.67% precision result for A₀

CHARITY: Chagas cardiomyopathy bisoprolol intervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]

BACKGROUND: Chagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected by T. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presenation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Beta-adrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy. METHODS/DESIGN: A cohort of 500 T. cruzi seropositive patients (250 per arm) will be selected from several institutions in Colombia. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms and baseline measurements and tests will be conducted including blood pressure measurements, twelve-lead ECG and left ventricular ejection fraction assessment by 2D echocardiography. Quality of life questionnaire will be performed two weeks apart during baseline examination using the "Minnesota living with heart failure" questionnaire. A minimum of two 6 minutes corridor walk test once a week over a two-week period will be performed to measure functional class. During the treatment period patients will be randomly assigned to receive Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5, 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. This study will allow us to explore the effect of beta-blockers in chagas' cardiomyopathy