Persistence of somatostatinergic tone in acromegaly

It is a matter of debate whether hypothalamic somatostatin (SRIH) secretion in acromegaly is preserved and still regulated by the physiological feedback mechanisms of growth hormone (GH) and insulin-like growth factor I. To gather further information on this, the reproducibility of plasma GH changes induced by growth hormone-releasing hormone (GHRH) administration was evaluated in 15 acromegalic patients. There was a highly significant correlation between the peak/basal ratio (P/B) GH response in the 15 patients administered GHRH on two separate occasions (r = 0.99, p < 0.001). The test was performed also before and after the administration of drugs able to inhibit or stimulate hypothalamic SRIH release, by activating (pyridostigmine) or inhibiting (pirenzepine) cholinergic pathways, respectively. The GHRH-induced GH response (P/B = 2, range 1.1-26.1) was increased significantly by pyridostigmine pretreatment in 30 patients (P/B = 2.6, range 1.3-34.8; p = 0.0045). In nine out of 30 patients an increase of greater than 2 SD of within-subject GHRH variability was observed in response to GHRH plus pyridostigmine when compared to GHRH alone. An inverse correlation (r = -0.37, p < 0.05) was observed between GH response to GHRH alone and after pyridostigmine pretreatment. On the contrary, no change of GHRH-induced GH response was observed in 12 patients after pirenzepine pretreatment (P/B = 1.9, range 1.1-5 and P/B = 2, range 1.3-6 without and after pirenzepine pretreatment, respectively). These data suggest that in acromegaly the somatostatinergic tone does not seem to fluctuate, and that it can be inhibited often by cholinergic pathway activation but not increased further by cholinergic suppression

Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus

β-Dystroglycan (β-DG) is a transmembrane protein with critical roles in cell adhesion, cytoskeleton remodeling and nuclear architecture. This functional diversity is attributed to the ability of β-DG to target to, and conform specific protein assemblies at the plasma membrane (PM) and nuclear envelope (NE). Although a classical NLS and importin α/β mediated nuclear import pathway has already been described for β-DG, the intracellular trafficking route by which β-DG reaches the nucleus is unknown. In this study, we demonstrated that β-DG undergoes retrograde intracellular trafficking from the PM to the nucleus via the endosome-ER network. Furthermore, we provided evidence indicating that the translocon complex Sec61 mediates the release of β-DG from the ER membrane, making it accessible for importins and nuclear import. Finally, we show that phosphorylation of β-DG at Tyr890 is a key stimulus for β-DG nuclear translocation. Collectively our data describe the retrograde intracellular trafficking route that β-DG follows from PM to the nucleus. This dual role for a cell adhesion receptor permits the cell to functionally connect the PM with the nucleus and represents to our knowledge the first example of a cell adhesion receptor exhibiting retrograde nuclear trafficking and having dual roles in PM and NE

Exploring cosmic origins with CORE : Inflation

We forecast the scientific capabilities to improve our understanding of cosmic inflation of CORE, a proposed CMB space satellite submitted in response to the ESA fifth call for a medium-size mission opportunity. The CORE satellite will map the CMB anisotropies in temperature and polarization in 19 frequency channels spanning the range 60-600 GHz. CORE will have an aggregate noise sensitivity of 1.7 mu K.arcmin and an angular resolution of 5' at 200 GHz. We explore the impact of telescope size and noise sensitivity on the inflation science return by making forecasts for several instrumental configurations. This study assumes that the lower and higher frequency channels suffice to remove foreground contaminations and complements other related studies of component separation and systematic effects, which will be reported in other papers of the series "Exploring Cosmic Origins with CORE." We forecast the capability to determine key inflationary parameters, to lower the detection limit for the tensor-to-scalar ratio down to the 10(-3) level, to chart the landscape of single field slow-roll inflationary models, to constrain the epoch of reheating, thus connecting inflation to the standard radiation-matter dominated Big Bang era, to reconstruct the primordial power spectrum, to constrain the contribution from isocurvature perturbations to the 10(-3) level, to improve constraints on the cosmic string tension to a level below the presumptive GUT scale, and to improve the current measurements of primordial non-Gaussianities down to the f(NL)(local) <1 level. For all the models explored, CORE alone will improve significantly on the present constraints on the physics of inflation. Its capabilities will be further enhanced by combining with complementary future cosmological observations.Peer reviewe

Euclid preparation: XXX. Performance assessment of the NISP red grism through spectroscopic simulations for the wide and deep surveys

This work focusses on the pilot run of a simulation campaign aimed at investigating the spectroscopic capabilities of the Euclid Near-Infrared Spectrometer and Photometer (NISP), in terms of continuum and emission line detection in the context of galaxy evolutionary studies. To this purpose, we constructed, emulated, and analysed the spectra of 4992 star-forming galaxies at 0:3 ≥ z ≥ 2:5 using the NISP pixel-level simulator. We built the spectral library starting from public multi-wavelength galaxy catalogues, with value-added information on spectral energy distribution (SED) fitting results, and stellar population templates from Bruzual & Charlot (2003, MNRAS, 344, 1000). Rest-frame optical and near-IR nebular emission lines were included using empirical and theoretical relations. Dust attenuation was treated using the Calzetti extinction law accounting for the differential attenuation in line-emitting regions with respect to the stellar continuum. The NISP simulator was configured including instrumental and astrophysical sources of noise such as the dark current, read-out noise, zodiacal background, and out-of-field stray light. In this preliminary study, we avoided contamination due to the overlap of the slitless spectra. For this purpose, we located the galaxies on a grid and simulated only the first order spectra.We inferred the 3.5δ NISP red grism spectroscopic detection limit of the continuum measured in the H band for star-forming galaxies with a median disk half-light radius of 0: 004 at magnitude H = 19:5 = 0:2ABmag for the Euclid Wide Survey and at H = 20:8 = 0:6ABmag for the Euclid Deep Survey. We found a very good agreement with the red grism emission line detection limit requirement for the Wide and Deep surveys. We characterised the effect of the galaxy shape on the detection capability of the red grism and highlighted the degradation of the quality of the extracted spectra as the disk size increased. In particular, we found that the extracted emission line signal-to-noise ratio (S/N) drops by 45% when the disk size ranges from 0: 0025 to 100. These trends lead to a correlation between the emission line S/N and the stellar mass of the galaxy and we demonstrate the effect in a stacking analysis unveiling emission lines otherwise too faint to detect

Planck 2018 results. IV. Diffuse component separation

We present full-sky maps of the cosmic microwave background (CMB) and polarized synchrotron and thermal dust emission, derived from the third set of Planck frequency maps. These products have significantly lower contamination from instrumental systematic effects than previous versions. The methodologies used to derive these maps follow closely those described in earlier papers, adopting four methods (Commander, NILC, SEVEM, and SMICA) to extract the CMB component, as well as three methods (Commander, GNILC, and SMICA) to extract astrophysical components. Our revised CMB temperature maps agree with corresponding products in the Planck 2015 delivery, whereas the polarization maps exhibit significantly lower large-scale power, reflecting the improved data processing described in companion papers; however, the noise properties of the resulting data products are complicated, and the best available end-to-end simulations exhibit relative biases with respect to the data at the few percent level. Using these maps, we are for the first time able to fit the spectral index of thermal dust independently over 3 degree regions. We derive a conservative estimate of the mean spectral index of polarized thermal dust emission of beta_d = 1.55 +/- 0.05, where the uncertainty marginalizes both over all known systematic uncertainties and different estimation techniques. For polarized synchrotron emission, we find a mean spectral index of beta_s = -3.1 +/- 0.1, consistent with previously reported measurements. We note that the current data processing does not allow for construction of unbiased single-bolometer maps, and this limits our ability to extract CO emission and correlated components. The foreground results for intensity derived in this paper therefore do not supersede corresponding Planck 2015 products. For polarization the new results supersede the corresponding 2015 products in all respects

Exploring Cosmic Origins with CORE: Survey requirements and mission design

Future observations of cosmic microwave background (CMB) polarisation havethe potential to answer some of the most fundamental questions of modernphysics and cosmology. In this paper, we list the requirements for a future CMBpolarisation survey addressing these scientific objectives, and discuss thedesign drivers of the CORE space mission proposed to ESA in answer to the "M5"call for a medium-sized mission. The rationale and options, and themethodologies used to assess the mission's performance, are of interest toother future CMB mission design studies. CORE is designed as a near-ultimateCMB polarisation mission which, for optimal complementarity with ground-basedobservations, will perform the observations that are known to be essential toCMB polarisation scienceand cannot be obtained by any other means than adedicated space mission

Planck 2018 results: IX. Constraints on primordial non-Gaussianity

We analyse the Planck full-mission cosmic microwave background (CMB) temperature and E-mode polarization maps to obtain constraints on primordial non-Gaussianity (NG). We compare estimates obtained from separable template-fitting, binned, and optimal modal bispectrum estimators, finding consistent values for the local, equilateral, and orthogonal bispectrum amplitudes. Our combined temperature and polarization analysis produces the following final results: flocalNL= -0.9 \ub1 5.1; fequilNL= -26 \ub1 47; and forthoNL= -38 \ub1 24 (68% CL, statistical). These results include low-multipole (4 64 \u2113 &lt; 40) polarization data that are not included in our previous analysis. The results also pass an extensive battery of tests (with additional tests regarding foreground residuals compared to 2015), and they are stable with respect to our 2015 measurements (with small fluctuations, at the level of a fraction of a standard deviation, which is consistent with changes in data processing). Polarizationonly bispectra display a significant improvement in robustness; they can now be used independently to set primordial NG constraints with a sensitivity comparable to WMAP temperature-based results and they give excellent agreement. In addition to the analysis of the standard local, equilateral, and orthogonal bispectrum shapes, we consider a large number of additional cases, such as scale-dependent feature and resonance bispectra, isocurvature primordial NG, and parity-breaking models, where we also place tight constraints but do not detect any signal. The nonprimordial lensing bispectrum is, however, detected with an improved significance compared to 2015, excluding the null hypothesis at 3.5\u3c3. Beyond estimates of individual shape amplitudes, we also present model-independent reconstructions and analyses of the Planck CMB bispectrum. Our final constraint on the local primordial trispectrum shape is glocalNL= (-5.8 \ub1 6.5) 7 104(68% CL, statistical), while constraints for other trispectrum shapes are also determined. Exploiting the tight limits on various bispectrum and trispectrum shapes, we constrain the parameter space of different early-Universe scenarios that generate primordial NG, including general single-field models of inflation, multi-field models (e.g. curvaton models), models of inflation with axion fields producing parity-violation bispectra in the tensor sector, and inflationary models involving vector-like fields with directionally-dependent bispectra. Our results provide a high-precision test for structure-formation scenarios, showing complete agreement with the basic picture of the CDM cosmology regarding the statistics of the initial conditions, with cosmic structures arising from adiabatic, passive, Gaussian, and primordial seed perturbations

Exploring cosmic origins with CORE: Survey requirements and mission design

Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology. In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the CORE space mission proposed to ESA in answer to the "M5" call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. CORE is designed as a near-ultimate CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation scienceand cannot be obtained by any other means than a dedicated space mission.Comment: 79 pages, 14 figure

Enzymatic resolution of 3-butene-1,2-diol in organic solvents and optimization of reaction conditions

Lipases from different sources were tested in the kinetic resolution of 2-hydroxy-3-butenyl butanoate {[(R,S)-2] carried out by transesterification of the secondary alcohol. The influence of organic solvent. acyl donor and temperature on the enantioselectivity and activity of lipases was also investigated. Our study showed that both R-(+)-2 and S-(-)-2 could be obtained in high enantiomeric purity (ee greater than or equal to 99\%) and satisfactory yield (29\% and 27\%, respectively). Among the enzymes tested, lipase from Candida antarctica B (CALB) showed the highest preference for the (R)-enantiomer (E = 26 at -13 degrees C), whereas lipase from Pseudomonas fluorescens (lipase AK) acylated the (S)-enantiomer preferentially (E = 18 at -9 degrees C).