Molecular, Biochemical and Genetic Characteristics of BSE in Canada

The epidemiology and possibly the etiology of bovine spongiform encephalopathy (BSE) have recently been recognized to be heterogeneous. In particular, three types [classical (C) and two atypical (H, L)] have been identified, largely on the basis of characteristics of the proteinase K (PK)-resistant core of the misfolded prion protein associated with the disease (PrPres). The present study was conducted to characterize the 17 Canadian BSE cases which occurred prior to November 2009 based on the molecular and biochemical properties of their PrPres, including immunoreactivity, molecular weight, glycoform profile and relative PK sensitivity. Two cases exhibited molecular weight and glycoform profiles similar to those of previously reported atypical cases, one corresponding to H-type BSE (case 6) and the other to L-type BSE (case 11). All other cases were classified as C-type. PK digestion under mild and stringent conditions revealed a reduced protease resistance in both of these cases compared to the C-type cases. With Western immunoblotting, N-terminal-specific antibodies bound to PrPres from case 6 but not to that from case 11 or C-type cases. C-terminal-specific antibodies revealed a shift in the glycoform profile and detected a fourth protein fragment in case 6, indicative of two PrPres subpopulations in H-type BSE. No mutations suggesting a genetic etiology were found in any of the 17 animals by sequencing the full PrP-coding sequence in exon 3 of the PRNP gene. Thus, each of the three known BSE types have been confirmed in Canadian cattle and show molecular characteristics highly similar to those of classical and atypical BSE cases described from Europe, Japan and the USA. The occurrence of atypical cases of BSE in countries such as Canada with low BSE prevalence and transmission risk argues for the occurrence of sporadic forms of BSE worldwide

Glucokinase (GCK) Mutations and Their Characterization in MODY2 Children of Southern Italy

Type 2 Maturity Onset Diabetes of the Young (MODY2) is a monogenic autosomal disease characterized by a primary defect in insulin secretion and hyperglycemia. It results from GCK gene mutations that impair enzyme activity. Between 2006 and 2010, we investigated GCK mutations in 66 diabetic children from southern Italy with suspected MODY2. Denaturing High Performance Liquid Chromatography (DHPLC) and sequence analysis revealed 19 GCK mutations in 28 children, six of which were novel: p.Glu40Asp, p.Val154Leu, p.Arg447Glyfs, p.Lys458_Cys461del, p.Glu395_Arg397del and c.580-2A>T. We evaluated the effect of these 19 mutations using bioinformatic tools such as Polymorphism Phenotyping (Polyphen), Sorting Intolerant From Tolerant (SIFT) and in silico modelling. We also conducted a functional study to evaluate the pathogenic significance of seven mutations that are among the most severe mutations found in our population, and have never been characterized: p.Glu70Asp, p.His137Asp, p.Phe150Tyr, p.Val154Leu, p.Gly162Asp, p.Arg303Trp and p.Arg392Ser. These seven mutations, by altering one or more kinetic parameters, reduced enzyme catalytic activity by >40%. All mutations except p.Glu70Asp displayed thermal-instability, indeed >50% of enzyme activity was lost at 50°C/30 min. Thus, these seven mutations play a pathogenic role in MODY2 insurgence. In conclusion, this report revealed six novel GCK mutations and sheds some light on the structure-function relationship of human GCK mutations and MODY2

Exploring the Solar Wind from Its Source on the Corona into the Inner Heliosphere during the First Solar Orbiter-Parker Solar Probe Quadrature

This Letter addresses the first Solar Orbiter (SO)–Parker Solar Probe (PSP) quadrature, occurring on 2021 January 18 to investigate the evolution of solar wind from the extended corona to the inner heliosphere. Assuming ballistic propagation, the same plasma volume observed remotely in the corona at altitudes between 3.5 and 6.3 solar radii above the solar limb with the Metis coronagraph on SO can be tracked to PSP, orbiting at 0.1 au, thus allowing the local properties of the solar wind to be linked to the coronal source region from where it originated. Thanks to the close approach of PSP to the Sun and the simultaneous Metis observation of the solar corona, the flow-aligned magnetic field and the bulk kinetic energy flux density can be empirically inferred along the coronal current sheet with an unprecedented accuracy, allowing in particular estimation of the Alfvén radius at 8.7 solar radii during the time of this event. This is thus the very first study of the same solar wind plasma as it expands from the sub-Alfvénic solar corona to just above the Alfvén surface

Dynamical Evolution of Planetary Systems

Planetary systems can evolve dynamically even after the full growth of the planets themselves. There is actually circumstantial evidence that most planetary systems become unstable after the disappearance of gas from the protoplanetary disk. These instabilities can be due to the original system being too crowded and too closely packed or to external perturbations such as tides, planetesimal scattering, or torques from distant stellar companions. The Solar System was not exceptional in this sense. In its inner part, a crowded system of planetary embryos became unstable, leading to a series of mutual impacts that built the terrestrial planets on a timescale of ~100 My. In its outer part, the giant planets became temporarily unstable and their orbital configuration expanded under the effect of mutual encounters. A planet might have been ejected in this phase. Thus, the orbital distributions of planetary systems that we observe today, both solar and extrasolar ones, can be different from the those emerging from the formation process and it is important to consider possible long-term evolutionary effects to connect the two.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H. Deeg & J.A. Belmont

Data monitoring roadmap. The experience of the Italian Multiple Sclerosis and Related Disorders Register

Introduction Over the years, disease registers have been increasingly considered a source of reliable and valuable population studies. However, the validity and reliability of data from registers may be limited by missing data, selection bias or data quality not adequately evaluated or checked.This study reports the analysis of the consistency and completeness of the data in the Italian Multiple Sclerosis and Related Disorders Register.MethodsThe Register collects, through a standardized Web-based Application, unique patients.Data are exported bimonthly and evaluated to assess the updating and completeness, and to check the quality and consistency. Eight clinical indicators are evaluated.ResultsThe Register counts 77,628 patients registered by 126 centres. The number of centres has increased over time, as their capacity to collect patients.The percentages of updated patients (with at least one visit in the last 24 months) have increased from 33% (enrolment period 2000-2015) to 60% (enrolment period 2016-2022). In the cohort of patients registered after 2016, there were >= 75% updated patients in 30% of the small centres (33), in 9% of the medium centres (11), and in all the large centres (2).Clinical indicators show significant improvement for the active patients, expanded disability status scale every 6 months or once every 12 months, visits every 6 months, first visit within 1 year and MRI every 12 months.ConclusionsData from disease registers provide guidance for evidence-based health policies and research, so methods and strategies ensuring their quality and reliability are crucial and have several potential applications

Euclid: Covariance of weak lensing pseudo-C_ell estimates. Calculation, comparison to simulations, and dependence on survey geometry

An accurate covariance matrix is essential for obtaining reliable cosmological results when using a Gaussian likelihood. In this paper we study the covariance of pseudo-C_ estimates of tomographic cosmic shear power spectra. Using two existing publicly available codes in combination, we calculate the full covariance matrix, including mode-coupling contributions arising from both partial sky coverage and non-linear structure growth. For three different sky masks, we compare the theoretical covariance matrix to that estimated from publicly available N-body weak lensing simulations, finding good agreement. We find that as a more extreme sky cut is applied, a corresponding increase in both Gaussian off-diagonal covariance and non-Gaussian super-sample covariance is observed in both theory and simulations, in accordance with expectations. Studying the different contributions to the covariance in detail, we find that the Gaussian covariance dominates along the main diagonal and the closest off-diagonals, but further away from the main diagonal the super-sample covariance is dominant. Forming mock constraints in parameters describing matter clustering and dark energy, we find that neglecting non-Gaussian contributions to the covariance can lead to underestimating the true size of confidence regions by up to 70 per cent. The dominant non-Gaussian covariance component is the super-sample covariance, but neglecting the smaller connected non-Gaussian covariance can still lead to the underestimation of uncertainties by 10--20 per cent. A real cosmological analysis will require marginalisation over many nuisance parameters, which will decrease the relative importance of all cosmological contributions to the covariance, so these values should be taken as upper limits on the importance of each component

Non-canonical amino acids bearing thiophene and bithiophene: synthesis by an Ugi multicomponent reaction and studies on ion recognition ability

Novel thienyl and bithienyl amino acids with different substituents were obtained by a multicomponent Ugi reaction between a heterocyclic aldehyde, an amine, an acid and an isocyanide. Due to the presence of the sulphur heterocycle at the side chain, these unnatural amino acids are highly emissive and bear extra electron donating atoms so they were tested for their ability to act as fluorescent probes and chemosensors in the recognition of biomedically relevant ions in acetonitrile and acetonitrile/water solutions. The results obtained from spectrophotometric/spectrofluorimetric titrations in the presence of organic and inorganic anions, and alkaline; alkaline-earth and transition metal cations indicated that the bithienyl amino acid bearing a methoxy group is a selective colorimetric chemosensor for Cu2+, while the other (bi)thienyl amino acids act as fluorimetric chemosensors with high sensitivity towards Fe3+ and Cu2+ in a metal-ligand complex with 1:2 stoichiometry. The photophysical and ion sensing properties of these amino acids confirm their potential as fluorescent probes suitable for incorporation into peptidic frameworks with chemosensory ability.Thanks are due to Fundação para a Ciência e Tecnologia (FCT-Portugal) and FEDER-COMPETE for financial support through Centro de Química [PEst-C/QUI/UI0686/2013 (F-COMP-01-0124-FEDER-037302)] and a PhD grant to C.I.C. Esteves (SFRH/BD/68360/2010). The NMR spectrometer Bruker Avance III 400 is part of the National NMR Network and was purchased with funds from FCT and FEDER.info:eu-repo/semantics/publishedVersio

Euclid preparation: XXXVI. Modelling the weak lensing angular power spectrum

This work considers which higher order modeling effects on the cosmic shear angular power spectra must be taken into account for Euclid. We identified the relevant terms and quantified their individual and cumulative impact on the cosmological parameter inferences from Euclid. We computed the values of these higher order effects using analytic expressions and calculated the impact on cosmological parameter estimations using the Fisher matrix formalism. We reviewed 24 effects and determined the ones that potentially need to be accounted for, namely: the reduced shear approximation, magnification bias, source-lens clustering, source obscuration, local Universe effects, and the flat Universe assumption. After computing these effects explicitly and calculating their cosmological parameter biases, using a maximum multipole of ℓ = 5000, we find that the magnification bias, source-lens clustering, source obscuration, and local Universe terms individually produce significant (> 0.25σ) cosmological biases in one or more parameters; accordingly, these effects must be accounted for and warrant further investigation. In total, we find biases in Ωm, Ωb, h, and σ8 of 0.73σ, 0.28σ, 0.25σ, and −0.79σ, respectively, for the flat ΛCDM. For the w0waCDM case, we found biases in Ωm, Ωb, h, ns, σ8, and wa of 1.49σ, 0.35σ, −1.36σ, 1.31σ, −0.84σ, and −0.35σ, respectively. These are increased relative to the ΛCDM due to additional degeneracies as a function of redshift and scale

Euclid preparation: LIX. Angular power spectra from discrete observations

In this paper we present the framework for measuring angular power spectra in the Euclid mission. The observables in galaxy surveys, such as galaxy clustering and cosmic shear, are not continuous fields, but discrete sets of data, obtained only at the positions of galaxies. We show how to compute the angular power spectra of such discrete data sets, without treating observations as maps of an underlying continuous field that is overlaid with a noise component. This formalism allows us to compute the exact theoretical expectations for our measured spectra, under a number of assumptions that we track explicitly. In particular, we obtain exact expressions for the additive biases (‘shot noise’) in angular galaxy clustering and cosmic shear. For efficient practical computations, we introduce a spin-weighted spherical convolution with a well-defined convolution theorem, which allows us to apply exact theoretical predictions to finite-resolution maps, including HEALPix. When validating our methodology, we find that our measurements are biased by less than 1% of their statistical uncertainty in simulations of Euclid’s first data release