The earliest site of iodination in thyroglobulin is residue number 5.

In most highly structured native proteins, as well as in thyroglobulin, the reactivity in vitro of the various tyrosyl residues toward iodine is widely different. The present work demonstrates that of nearly 70 tyrosyl residues present in rat thyroglobulin, there is one, residue number 5 from the NH2-terminal end, which has in vivo the highest affinity toward iodine, being the first one to be iodinated. In fact, when 6-(n-propyl)-2-thiouracil (PTU)-treated, iodine-deficient animals were injected with 125I and killed shortly after, we isolated from thyroid glands poorly iodinated thyroglobulin (about 1 iodine atom/thyroglobulin molecule), nearly 90% of the radioactivity of which was found as monoiodotyrosine. Although CNBr cleavage of this protein gave several fragments after gel electrophoresis only one of these, with apparent mass 27,000 Da, contained 125I. This fragment was isolated and fully characterized. Twelve cycles of automated Edman degradation were performed; the sequence found, i.e. N-I-F-E-X-Q-V-X-A-Q-X-L, indicated that the 27,000-Da fragment is the NH2 terminus of thyroglobulin. This portion of the polypeptide chain contains several tyrosyl residues which may well all be potentially involved in the early iodination of the protein. The observation that the removal of seven amino acids from the NH2 terminus is accompanied (at the fifth step) by the total disappearance of radioactivity in the resulting shortened peptide suggested that the fifth residue was the only one iodinated under these conditions. A second, more quantitative experiment was performed on thyroglobulin obtained from 6-(n-propyl)-2-thiouracil-treated animals whose death was postponed 24 h after the injection of 125I. In this case the radioactivity was found not only in a single CNBr fragment (27,000 Da) but also in other discrete species of lower molecular mass. The mixture of these peptides was subjected to seven steps of manual Edman degradation. Fragments before and after partial degradation were run in parallel on a polyacrylamide gel and the distribution of 125I compared. Besides some change in the background, the two profiles were identical except for the absence of the 27,000-Da species. This proves that all the 125I present in the 27,000-Da species was localized at the fifth residue, the same site at which the hormone molecule is preferentially synthesized under normal conditions. This result is not unexpected and is in accord with the known properties of thyroglobulin which has a polypeptide chain designed for efficient synthesis of the hormone even at low levels of iodination

Identification of hormonogenic tyrosines in fragment 1218-1591 of bovine thyroglobulin by mass spectrometry. Hormonogenic acceptor TYR-12donor TYR-1375.

A fragment of bovine thyroglobulin encompassing residues 1218-1591 was prepared by limited proteolysis with thermolysin and continuous-elution polyacrylamide gel electrophoresis in SDS. The reduced and carboxymethylated peptide was digested with endoproteinase Asp-N and fractionated by reverse-phase high performance liquid chromatography. The fractions were analyzed by electrospray and fast atom bombardment mass spectrometry in combination with Edman degradation. The post-translational modifications of all seven tyrosyl residues of the fragment were characterized at an unprecedented level of definition. The analysis revealed the formation of: 1) monoiodotyrosine from tyrosine 1234; 2) monoiodotyrosine, diiodotyrosine, triiodothyronine (T3), and tetraiodothyronine (thyroxine, T4) from tyrosine 1291; and 3) monoiodotyrosine, diiodotyrosine, and dehydroalanine from tyrosine 1375. Iodothyronine formation from tyrosine 1291 accounted for 10% of total T4 of thyroglobulin (0.30 mol of T4/mol of 660-kDa thyroglobulin), and 8% of total T3 (0.08 mol of T3/mol of thyroglobulin). This is the first documentation of the hormonogenic nature of tyrosine 1291 of bovine thyroglobulin, as thyroxine formation at a corresponding site was so far reported only in rabbit, guinea pig, and turtle thyroglobulin. This is also the first direct identification of tyrosine 1375 of bovine thyroglobulin as a donor residue. It is suggested that tyrosyl residues 1291 and 1375 may support together the function of an independent hormonogenic domain in the mid-portion of the polypeptide chain of thyroglobulin

Case-based learning. A formal approach to generate health case studies from electronic healthcare records

There is an increasing social pressure to train medical students with a level of competency sufficient to face clinical practice already at the end of their curriculum. The case-based learning (CBL) is an efficient teaching method to prepare students for clinical practice through the use of real or realistic clinical cases. In this regard, the Electronic Healthcare Record (EHR) could be a good source of real patient stories that can be transformed into educative cases. In this paper a formal approach to generate Health Case Studies from EHR is defined

Predicting mid-air gestural interaction with public displays based on audience behaviour

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.Knowledge about the expected interaction duration and expected distance from which users will interact with public displays can be useful in many ways. For example, knowing upfront that a certain setup will lead to shorter interactions can nudge space owners to alter the setup. If a system can predict that incoming users will interact at a long distance for a short amount of time, it can accordingly show shorter versions of content (e.g., videos/advertisements) and employ at-a-distance interaction modalities (e.g., mid-air gestures). In this work, we propose a method to build models for predicting users’ interaction duration and distance in public display environments, focusing on mid-air gestural interactive displays. First, we report our findings from a field study showing that multiple variables, such as audience size and behaviour, significantly influence interaction duration and distance. We then train predictor models using contextual data, based on the same variables. By applying our method to a mid-air gestural interactive public display deployment, we build a model that predicts interaction duration with an average error of about 8 s, and interaction distance with an average error of about 35 cm. We discuss how researchers and practitioners can use our work to build their own predictor models, and how they can use them to optimise their deployment.Peer reviewe

Surveying, modeling and communication techniques for the documentation of medieval wooden painted ceilings in the Mediterranean area

Wooden painted ceilings of the Mediterranean area in the middle age have their origin in the islamic culture and were then spread in the countries under the dominion of the Arabs; some of the surviving ceilings are now located in Sicily and Spain. In the historic centre of Palermo two well preserved medieval ceilings are still surviving; the first, built in the XII century, is located in the Palatine chapel; the second one, built in the XIV century covers the “Sala Magna” in the Steri of Palermo. The research, focused on the ceiling in the Steri, deals with the definition of a process for the integration of surveying techniques (photogrammetry, laser scanning), modelling processes and communication technologies for the documentation of such artefacts. The documentation of painted ceilings requires the strict integration of photographic and 3D metric data; the existing documentation is usually made of documents (drawings, photographs) that keep geometric and metric data separated from the photographic documentation of the paintings. The first stage in this work is therefore addressed to produce a digital document that combines metric and photographic data in a 3D textured model; in the second stage a vocal guide interacting with the 3D model has been developed; such guide, thought as a support to people visiting the Steri, uses a database with historic contents and symbolic interpretation of the painted scenes to answer specific questions and “take” the visitor close to the related paintings

Information in a network of neuronal cells: Effect of cell density and short-term depression

Neurons are specialized, electrically excitable cells which use electrical to chemical signals to transmit and elaborate information. Understanding how the cooperation of a great many of neurons in a grid may modify and perhaps improve the information quality, in contrast to few neurons in isolation, is critical for the rational design of cell-materials interfaces for applications in regenerative medicine, tissue engineering, and personalized lab-on-a-chips. In the present paper, we couple an integrate-and-fire model with information theory variables to analyse the extent of information in a network of nerve cells. We provide an estimate of the information in the network in bits as a function of cell density and short-term depression time. In the model, neurons are connected through a Delaunay triangulation of not-intersecting edges; in doing so, the number of connecting synapses per neuron is approximately constant to reproduce the early time of network development in planar neural cell cultures. In simulations where the number of nodes is varied, we observe an optimal value of cell density for which information in the grid is maximized. In simulations in which the posttransmission latency time is varied, we observe that information increases as the latency time decreases and, for specific configurations of the grid, it is largely enhanced in a resonance effect

DEVICE FOR OBTAINING THREE-DIMENSIONAL CELL CULTURES, METHOD FOR THE IMPLEMENTATION THEREOF, AND USE OF SUCH DEVICE

A device for obtaining threedimensional cell cultures comprising: a sub strate (1); a plurality of micro-structures (2) which protrude from the surface of the sub strate (1) and are arranged on such substrate (1) according to a periodical grid so as to make the substrate (1) super hydrophobic. The device is characterised in that the micro-struc tures (2) have side walls at least partially nano-patterned and have projections (14) and recesses (16) alternated with a predetermined distance

A Systematic Review and Exploratory Meta-Analysis

The relationship between antiphospholipid antibodies (aPL) and sickle cell disease (SCD) has never been systematically addressed. Our aim was to evaluate potential links between SCD and aPL in all age groups. EMBASE/PubMed was screened from inception to May 2020 and Peto odds ratios for rare events were calculated. The pooled prevalence (PP) of IgG anticardiolipin antibodies (aCL) was higher in individuals with SCD than in controls (27.9% vs 8.7%, P < 0.0001), that of IgM aCL was similar in the two groups (2.9% vs 2.7%); only individuals with SCD were positive for lupus anticoagulant (LA) (7.7% vs 0%, P < 0.0001). The PP of leg ulcers was similar between aPL positive and negative individuals (44% vs 53%) and between patients in acute crisis and stable patients (5.6% vs 7.3%). Reporting of aPL as a binary outcome and not as a titer precluded further interpretation. The results indicate that a prospective case-control study with serial measurements of a panel of aPL in SCD patients might be warranted, in order to understand further the possible pathogenic role of aPL in SCD.publishersversionpublishe