J R SOC INTERFACE

Enzymes are dynamic entities, and their dynamic properties are clearly linked to their biological function. It follows that dynamics ought to play an essential role in enzyme evolution. Indeed, a link between conformational diversity and the emergence of new enzyme functionalities has been recognized for many years. However, it is only recently that state-of-the-art computational and experimental approaches are revealing the crucial molecular details of this link. Specifically, evolutionary trajectories leading to functional optimization for a given host environment or to the emergence of a new function typically involve enriching catalytically competent conformations and/or the freezing out of non-competent conformations of an enzyme. In some cases, these evolutionary changes are achieved through distant mutations that shift the protein ensemble towards productive conformations. Multifunctional intermediates in evolutionary trajectories are probably multi-conformational, i.e. able to switch between different overall conformations, each competent for a given function. Conformational diversity can assist the emergence of a completely new active site through a single mutation by facilitating transition-state binding. We propose that this mechanism may have played a role in the emergence of enzymes at the primordial, progenote stage, where it was plausibly promoted by high environmental temperatures and the possibility of additional phenotypic mutationsDepartment of Chemistry, BMC, Uppsala University, Box 576, 751 23 Uppsala, Sweden Departamento de Quimica Fisica, Facultad de Ciencias, University of Granada, 18071 Granada, SpainWallenberg Academy Fellowship to S.C.L.K. from the Knut and Alice Wallenberg Foundation (KAW 2013.0124)Grant RGP0041/2017 from the Human Frontier Science ProgramFEDER Funds and grant BIO2015–66426-R to J.M.S.R. from the Spanish Ministry of Economy and Competitivenes

HEMIC Project: Design of a Clinical Information Modelling Tool Based on ISO13972 Technical Specification

The Andalusian Health Service is the public healthcare provider for 8.302.923 inhabitants in the South Spain. This organization coordinates primary and specialized care with an IT infrastructure composed by multiple Electronic Health Record Systems. According to the large volume of healthcare professionals involved, there is a need for providing a consistent management of information through multiple locations and systems. The HEMIC project aims to address this need developing and validating a methodology based on a software tool for standardizing information contained within EHR systems. The developed tool has been designed for supporting the participation of healthcare professionals the establishment of mechanisms for information governance. This research presents the requirements and designs for of a software tool focused on the adoption of recognized best practice in clinical information modeling. The designed tool has a Service Oriented Architecture that will be able to integrate terminology servers and repositories of clinical information models as part of the modeling process. Moreover, the defined tool organizes clinicians, IT developers and terminology experts involved in the modeling process in three levels to promote their coordination in the definition, specialization and validation of clinical information models. In order to ensure the quality of the developed clinical information models, the defined tool is based on the requirements defined in the ISO13972 Technical Specification

Evaluation of Linked Determinants Between Diabetes and Caries

Dental caries and diabetes mellitus, represent two chronic diseases of public health that present statistics of high prevalence worldwide. One of the main problems that affect these conditions is demography, since the least developed countries are those that have less access to public health services and are limited by the economic costs that represent the treatments. In this work is presented the univariate analysis, of a set of demographic determinants obtained from the National Health and Nutrition Examination Surveys (NHANES), in order to identify those that present the most significant information related to estimation of these diseases. According to the results, the age of the subjects is the main determinant describing the simultaneous presence of these diseases, obtaining an area under the curve (AUC) value ≥ 0.846, concluding that age can be used as tool for their preventive diagnosis

Pumped double quantum dot with spin-orbit coupling

We study driven by an external electric field quantum orbital and spin dynamics of electron in a one-dimensional double quantum dot with spin-orbit coupling. Two types of external perturbation are considered: a periodic field at the Zeeman frequency and a single half-period pulse. Spin-orbit coupling leads to a nontrivial evolution in the spin and orbital channels and to a strongly spin- dependent probability density distribution. Both the interdot tunneling and the driven motion contribute into the spin evolution. These results can be important for the design of the spin manipulation schemes in semiconductor nanostructures

Measurement of finite-frequency current statistics in a single-electron transistor

Electron transport in nano-scale structures is strongly influenced by the Coulomb interaction which gives rise to correlations in the stream of charges and leaves clear fingerprints in the fluctuations of the electrical current. A complete understanding of the underlying physical processes requires measurements of the electrical fluctuations on all time and frequency scales, but experiments have so far been restricted to fixed frequency ranges as broadband detection of current fluctuations is an inherently difficult experimental procedure. Here we demonstrate that the electrical fluctuations in a single electron transistor (SET) can be accurately measured on all relevant frequencies using a nearby quantum point contact for on-chip real-time detection of the current pulses in the SET. We have directly measured the frequency-dependent current statistics and hereby fully characterized the fundamental tunneling processes in the SET. Our experiment paves the way for future investigations of interaction and coherence induced correlation effects in quantum transport.Comment: 7 pages, 3 figures, published in Nature Communications (open access

VALORACIÓN NUTRICIONAL EN LACTANTES DE ENTRE 8 A 12 MESES DE VIDA

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman";} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Objective: The aim of this study was to analyze the diet of infants that receive supplemental breast milk, by way of a two-week survey on nutrition consumption, completed by the parents of infants between 8 and 12 months of age from the province of Badajoz, Spain. Dial® software was used for the nutritional analysis and quantification.  Results: The analysis of the daily diet shows in this study that it is repetitive and equivalent in all infants during this age interval, which is made: at the beginning of the day for follow-on milk and infantile cereals, followed by vegetable baby food with meat, fruit baby food, and finally at the end of the day follow-on milk and cereals again. Indicating that energy intake was correct (1355 ± 252.93 kcal), highlighting that regarding macronutrients the protein percentage intake (44.40 ± 5.014 g/day) is high compared to the daily recommendations. In addition, it presents a repetitive and constant dietary pattern throughout all the participants. Conclusion: In our study population with supplementary feeding, the diet of these infants between 8 and 12 months of age is suited to the daily energy needs for that period of growth, as well as an inadequate daily ingestion on proteins. .Objetivo: En este trabajo se ha tratado de conocer profundamente la alimentación infantil con lactancia complementaria, a través de un cuestionario de consumo de alimentos de dos semanas de duración, el cual fue completado por los padres de lactantes de entre 8 y 12 meses, de la provincia de Badajoz. Para su análisis y cuantificación nutricional se manejó la aplicación informática Dial©.  Resultados: El análisis de la dieta diaria mostró en su estudio que es repetitiva y equivalente en todos los lactantes durante este intervalo de edad, la cual estaba constituida: al inicio del día por leches de continuación y cereales infantiles, continuando con potitos de verduras con carne, potitos de fruta y por último al final del día, de nuevo leches de continuación y cereales infantiles. Indicar que la ingesta energética era correcta (1355 ± 252,93 kcal), destacando que en lo que respecta a macronutrientes el porcentaje en proteínas se encontró elevado (44,40 ± 5,014 g) frente a las recomendaciones diarias. Además de presentar un patrón dietético repetitivo y constante en toda la población. Conclusión: En la población estudiada con lactancia complementaria, la dieta de estos lactantes entre 8 y 12 meses de vida se adecua a las necesidades energéticas diarias para dicho periodo de crecimiento, pero mantienen una inadecuada ingesta diaria de proteínas

Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program

CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 22,311 GH-treated children from 827 investigative sites in 30 countries. PATIENTS: Children with growth disorders. INTERVENTIONS: GH treatment. MAIN OUTCOME MEASURES: Standardized mortality (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) for mortality, diabetes, and primary cancer, using general population registries. RESULTS: Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean±SD follow-up of 4.2±3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with SMR (95% CI) of 0.61 (0.44-0.82); the SMR was elevated for patients with cancer-related organic GH deficiency (5.87 [3.21-9.85]). Based on 18 cases, Type 2 diabetes (T2DM) risk was elevated (SIR 3.77 [2.24-5.96]), but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed (SIR 0.71 [0.39-1.20]). Second neoplasms occurred in 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared to the general population, but most cases had diabetes risk factors

Synthesis and Biological Evaluation of Phenanthrenes as Cytotoxic Agents with Pharmacophore Modeling and ChemGPS-NP Prediction as Topo II Inhibitors

In a structure-activity relationship (SAR) study, 3-methoxy-1,4-phenanthrenequinones, calanquinone A (6a), denbinobin (6b), 5-OAc-calanquinone A (7a) and 5-OAc-denbinobin (7b), have significantly promising cytotoxicity against various human cancer cell lines (IC50 0.08–1.66 µg/mL). Moreover, we also established a superior pharmacophore model for cytotoxicity (r = 0.931) containing three hydrogen bond acceptors (HBA1, HBA2 and HBA3) and one hydrophobic feature (HYD) against MCF-7 breast cancer cell line. The pharmacophore model indicates that HBA3 is an essential feature for the oxygen atom of 5-OH in 6a–b and for the carbonyl group of 5-OCOCH3 in 7a–b, important for their cytotoxic properties. The SAR for moderately active 5a–b (5-OCH3), and highly active 6a–b and 7a–b, are also elaborated in a spatial aspect model. Further rational design and synthesis of new cytotoxic phenanthrene analogs can be implemented via this model. Additionally, employing a ChemGPS-NP based model for cytotoxicity mode of action (MOA) provides support for a preliminary classification of compounds 6a–b as topoisomerase II inhibitors

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048

Caracterización fisicoquímica, actividad antioxidante y contenido de fenoles y flavonoides totales de nopal morado (Opuntia gosseliniana) en dos etapas de coloración

Nopal (Opuntia gosseliniana) is considered a food product of interest due to its functional properties, including its antioxidant activity. The objective of this work was to evaluate the physical-chemical properties (color, pH and total soluble solids), antioxidant activity (DPPH, ABTS and FRAP), content of total phenols and flavonoids and betalain content of ethanolic extracts of nopal in two stages of coloration: green and purple. The highest values for total phenols and flavonoids were found in the purple samples, with values of 2.31 mg EAG/gps and 3.06 mg EQ/gps, respectively. Similarly, in the antioxidant activity (in the three techniques used) and betalain content, higher values were obtained in the purple color stage. Therefore, this species of cacti could be a potential source of antioxidants and pigments of agroindustrial interest.El nopal (Opuntia gosseliniana) es considerado un producto alimenticio de interés debido a sus propiedades funcionales, incluyendo su actividad antioxidante. El objetivo de este trabajo fue evaluar las propiedades físico-químicas (color, pH y sólidos solubles totales), actividad antioxidante (DPPH, ABTS y FRAP), contenido de fenoles y flavonoides totales y contenido de betalaínas extractos etanólicos de nopal en dos etapas de coloración: verde y morado. Los valores más altos para fenoles y flavonoides totales se encontraron en las muestras de color morado, con valores de 2.31 mg EAG/gps y 3.06 mg EQ/gps, respectivamente. De igual manera, en la actividad antioxidante se obtuvieron valores más altos en la etapa de color morado en las tres técnicas utilizadas. Por lo que, esta especie de cactácea podría ser una fuente potencial de antioxidantes y pigmentos de interés agroindustrial