Directed evolution unlocks oxygen reactivity for a nicotine-degrading flavoenzyme.

The flavoenzyme nicotine oxidoreductase (NicA2) is a promising injectable treatment to aid in the cessation of smoking, a behavior responsible for one in ten deaths worldwide. NicA2 acts by degrading nicotine in the bloodstream before it reaches the brain. Clinical use of NicA2 is limited by its poor catalytic activity in the absence of its natural electron acceptor CycN. Without CycN, NicA2 is instead oxidized slowly by dioxygen (O2), necessitating unfeasibly large doses in a therapeutic setting. Here, we report a genetic selection strategy that directly links CycN-independent activity of NicA2 to growth of Pseudomonas putida S16. This selection enabled us to evolve NicA2 variants with substantial improvement in their rate of oxidation by O2. The encoded mutations cluster around a putative O2 tunnel, increasing flexibility and accessibility to O2 in this region. These mutations further confer desirable clinical properties. A variant form of NicA2 is tenfold more effective than the wild type at degrading nicotine in the bloodstream of rats.

Binding Interface and Electron Transfer Between Nicotine Oxidoreductase and Its Cytochrome c Electron Acceptor.

The enzyme nicotine oxidoreductase (NicA2) is a member of the flavoprotein amine oxidase family that uses a cytochrome c protein (CycN) as its oxidant instead of dioxygen, which is the oxidant used by most other members of this enzyme family. We recently identified a potential binding site for CycN on the surface of NicA2 through rigid body docking [J. Biol. Chem. 2022, 298 (8), 102251]. However, this potential binding interface has not been experimentally validated. In this paper, we used unnatural amino acid incorporation to probe the binding interface between NicA2 and CycN. Our results are consistent with a structural model of the NicA2-CycN complex predicted by protein-protein docking and AlphaFold, suggesting that this is the binding site for CycN on NicA2's surface. Based on additional mutagenesis of potentially redox active residues in NicA2, we propose that electron transfer from NicA2's flavin to CycN's heme occurs without the assistance of a protein-derived wire.

Glaciation as a destructive and constructive control on mountain building.

Theoretical analysis predicts that enhanced erosion related to late Cenozoic global cooling can act as a first-order influence on the internal dynamics of mountain building, leading to a reduction in orogen width and height. The strongest response is predicted in orogens dominated by highly efficient alpine glacial erosion, producing a characteristic pattern of enhanced erosion on the windward flank of the orogen and maximum elevation controlled by glacier equilibrium line altitude, where long-term glacier mass gain equals mass loss. However, acquiring definitive field evidence of an active tectonic response to global climate cooling has been elusive. Here we present an extensive new low-temperature thermochronologic data set from the Patagonian Andes, a high-latitude active orogen with a well-documented late Cenozoic tectonic, climatic and glacial history. Data from 38° S to 49° S record a marked acceleration in erosion 7 to 5 Myr ago coeval with the onset of major Patagonian glaciation and retreat of deformation from the easternmost thrust front. The highest rates and magnitudes of erosion are restricted to the glacial equilibrium line altitude on the windward western flank of the orogen, as predicted in models of glaciated critical taper orogens where erosion rate is a function of ice sliding velocity. In contrast, towards higher latitudes (49° S to 56° S) a transition to older bedrock cooling ages signifies much reduced late Cenozoic erosion despite dominantly glacial conditions here since the latest Miocene. The increased height of the orogenic divide at these latitudes (well above the equilibrium line altitude) leads us to conclude that the southernmost Patagonian Andes represent the first recognized example of regional glacial protection of an active orogen from erosion, leading to constructive growth in orogen height and width.

Nonlinear time-series forecasts for decision support: short-term demand for ICU beds in Santiago, Chile, during the 2021 COVID-19 pandemic.

In Chile, due to the explosive increase of new Coronavirus disease 2019 (COVID-19) cases during the first part of 2021, the ability of health services to accommodate new incoming cases was jeopardized. It has become necessary to be able to manage intensive care unit (ICU) capacity, and for this purpose, monitoring both the evolution of new cases and the demand for ICU beds has become urgent. This paper presents short-term forecast models for the number of new cases and the number of COVID-19 patients admitted to ICUs in the Metropolitan Region in Chile.

Forecasting the 2020 COVID-19 Epidemic: A Multivariate Quasi-Poisson Regression to Model the Evolution of New Cases in Chile.

Objectives: To understand and forecast the evolution of COVID-19 (Coronavirus disease 2019) in Chile, and analyze alternative simulated scenarios to better predict alternative paths, in order to implement policy solutions to stop the spread and minimize damage. Methods: We have specified a novel multi-parameter generalized logistic growth model, which does not only look at the trend of the data, but also includes explanatory covariates, using a quasi-Poisson regression specification to account for overdispersion of the count data. We fitted our model to data from the onset of the disease (February 28) until September 15. Estimating the parameters from our model, we predicted the growth of the epidemic for the evolution of the disease until the end of October 2020. We also evaluated via simulations different fictional scenarios for the outcome of alternative policies (those analyses are included in the Supplementary Material). Results and Conclusions: The evolution of the disease has not followed an exponential growth, but rather, stabilized and moved downward after July 2020, starting to increase again after the implementation of the Step-by-Step policy. The lockdown policy implemented in the majority of the country has proven effective in stopping the spread, and the lockdown-relaxation policies, however gradual, appear to have caused an upward break in the trend.

The Emotion Regulation Roots of Job Satisfaction.

Job satisfaction is a core variable in the study and practice of organizational psychology because of its implications for desirable work outcomes. Knowledge of its antecedents is abundant and informative, but there are still psychological processes underlying job satisfaction that have not received complete attention. This is the case of employee emotion regulation. In this study, we argue that employees' behaviors directed to manage their affective states participate in their level of job satisfaction and hypothesize that employee affect-improving and -worsening emotion regulation behaviors increase and decrease, respectively, job satisfaction, through the experience of positive and negative affect. Using a diary study with a sample of professionals from diverse jobs and organizations, for the most part, the mediational hypotheses were supported by the results albeit a more complex relationship was found in the case of affect worsening emotion regulation. This study contributes to expanding the job satisfaction and emotion regulation literatures and informs practitioners in people management in organizations about another route to foster and sustain positive attitudes at work.

Measurement of the Psychosocial Work Environment in Spanish: Validation of the Psychosocial Factors Questionnaire 75 (PSF-Q75) to Capture Demands and Resources at Different Levels of Analysis.

The psychological work environment is composed of both stressful and motivational work conditions at different levels of analysis. However, most relevant theory and research lack an integrative conceptualization and appropriate instrumentation to account for this work context structure. These limitations are particularly present in non-mainstream populations, such as the Spanish community of researchers and practitioners. In this study, based on the job demands-resources model, we present an updated conceptualization in which stressful and motivational psychosocial factors are integrated and defined at the job, the group, and the organizational level of analysis into a single conceptualization. Furthermore, derived from this conceptualization, we present a study of the development and validation of a questionnaire to account for the psychosocial work environment in Spanish, labeled Psychosocial Factors Questionnaire 75 (PSF-Q75), which provides measures for 23 different psychosocial factors. The results of this study supported the questionnaire's construct, convergent, divergent, and predictive validity, together with its reliability. Thus, this conceptualization and questionnaire provides researchers and partitioners with a more comprehensive approach to the assessment of the psychosocial work environment and promises benefits for interventions in the workplace.

Aspectos morfocuantitativos de las vellosidades coriales libres en gestas normales, con diabetes, hipertensión arterial y restricción del crecimiento intrauterino / Morphoquantitative characteristics of free corial vellosities in normal births, with diabetes, hypertension and restriction of intrauterine growth

Las patologías de la gestación como la hipertensión, diabetes mellitus gestacional, o restricción del crecimiento intrauterino, pueden determinar modificaciones en las características morfológicas macro y microscópicas de la placenta y sus vellosidades coriales libres, y en el feto se puede acompañar de manifestaciones patológicas, con riesgo para su calidad de vida futura, e incluso su viabilidad. El objetivo de este trabajo consistió en describir aspectos morfométricos e histológicos de las vellosidades coriales libres en gestas normales, con diabetes e hipertensión arterial. Se utilizaron 30 placentas humanas y fueron separadas, según presencia o ausencia de patologías en el embarazo, en tres grupos: Normal (N), Síndrome Hipertensivo del Embarazo (SHE), Diabetes (D) y Restricción del Crecimiento Intrauterino (RCIU). Se usó ficha para registrar peso placentario y del recién nacido Todas las muestras fueron fijadas en formalina tamponada al 10 %. De cada una fueron extraídas 5 muestras, obteniendo 25 cortes por cada placenta. Posteriormente, fueron teñidas con H&E, Azul Alcián y Tricrómico de Masson. Además, se efectuó el análisis histológico y morfométrico (ImageJ®) de las vellosidades coriales. El análisis estadístico fue realizado utilizando ANOVA. Entre los cambios morfológicos, se encontró una relación peso placentario/peso del recién nacido aumentada en la Diabetes Mellitus Gestacional asociada a cambios histológicos. No hubo cambios morfométricos significativos entre placentas N, SHE y D. Hubo un aumento en el número de vasos coriales en placentas del grupo D (P < 0,05) y de la superficie entre las vellosidades coriales. En el grupo SHE hubo aumento moderado de nudos sinciciales y presencia de fibrina en el estroma. Las placentas con Diabetes Mellitus Gestacional experimentan alteraciones histológicas, como consecuencia de cambios estructurales y funcionales. Además, el aumento de vasos sanguíneos en placentas con diabetes se produce por neoformación vascular y mayor penetración de vasos sanguíneos dentro de las vellosidades. En el caso del SHE las alteraciones placentarias se relacionan con la gravedad de la enfermedad.

Gestational pathologies such as hypertension, gestational diabetes mellitus and restriction of intrauterine growth can determine changes in the macro and microscopic morphological characteristics of the placenta and its free chorionic villi. In the fetus it can be accompanied by pathological manifestations with risk to its viability and future quality of life. The aim of this work was to describe morphometric and histological aspects of free chorionic villi in normal pregnancies associated with diabetes, hypertension and restriction of intrauterine growth. Thirty human placentas were used and were separated into three groups: Normal (N), Hypertensive Pregnancy Syndrome (SHE), Diabetes (D), and Restriction of Intrauterine Growth (RIG) according to evident pathologies or absence thereof during pregnancy. Tab was used to record placental and newborn weight. All samples were fixed in 10 % buffered formalin. From each, 5 samples were extracted, obtaining 25 cuts for each placenta. Subsequently, they were stained with H & E, Alcian Blue and Masson's Trichrome. In addition, histological and morphometric analysis (ImageJ®) of the chorion villus was carried out. Statistical analysis was performed using ANOVA. Among the morphological changes, an increased placental weight / weight ratio of the newborn was found in Gestational Diabetes Mellitus associated with histological changes. There were no significant morphometric changes between placentas N, SHE and D. There was an increase in the number of corial vessels in placentas of group D (P <0.05) and of the surface between the chorion villi. In the SHE group there was a moderate increase in syncytial nodes and presence of fibrin in the stroma. Placentas with Gestational Diabetes Mellitus experience histological alterations, as a consequence of structural and functional changes. In addition, the increase of blood vessels in placentas D is produced by vascular neoformation and increased penetration of blood vessels into the villi. In the case of SHE, placental alterations are related to the severity of the disease.

Empatía en estudiantes de medicina humana de la Universidad Nacional Pedro Ruiz Gallo. Mayo- Junio del 2011 / Empathy in medical students from the Universidad Nacional Pedro Ruiz Gallo: May- June 2011

Objetivo: Comparar los promedios de las puntuaciones de empatía en estudiantes de Medicina Humana de la Universidad Nacional Pedro Ruiz Gallo, según sexo, edad, año de estudios y especialidad médica a seguir. Material y Métodos: Estudio descriptivo transversal realizado en 183 estudiantes de medicina de la Universidad Nacional Pedro Ruiz Gallo. Se utilizó la Escala de Empatía Médica de Jefferson para medir la empatía; se realizó el análisis de datos con SPSS 19.0. Resultados: Se obtuvieron mayores puntuaciones de empatía en los hombres que en las mujeres. Al comparar los grupos de edad, estudiantes <25 años obtuvieron mayores puntuaciones que aquellos ≥25 años. Según el año de estudio, se encontraron mayores puntuaciones de empatía en los estudiantes de tercer año con relación a los de cuarto año y de sexto año. Especialidades "vinculadas al paciente" obtuvieron mayores puntuaciones que aquellas "no vinculadas al paciente". Además, 60 hombres (75%) y 66 estudiantes (82,5%) del grupo de edad <25 años alcanzaron niveles adecuados de empatía. Así mismo, 32 estudiantes (50,8%) de 3º año y 43 (53,8%) de especialidades "vinculadas al paciente" obtuvieron niveles adecuados de empatía. Conclusiones: Existen mayores puntuaciones de empatía en estudiantes varones, del grupo de edad <25 años, que cursan el 3º año y que eligieron especialidad "vinculadas al paciente", no hallándose significación estadística. Además, ser hombre, tener <25 años, cursar el 3º año y elegir especialidades "vinculadas al paciente", podría ser factor protector para desarrollar niveles adecuados de empatía, no hallándose intervalos de confianza significativos(AU)

Objective: To compare the mean scores of empathy in medicine students from the Universidad Nacional Pedro Ruiz Gallo, according to sex, age, year of study and medical especialty to follow. Methods: Cross- sectional descriptive study done in 183 medicine students from the Universidad Nacional Pedro Ruiz Gallo. The Jefferson Medical Empathy Scale was used to measure empathy, and data analysis was done using SPSS 19.0. Results: Greater empathy scores were obtained in men than in women. When comparing age groups, students <25 years obtained greater scores than those ≥25years. According to the year of study, we found greater empathy scores in third year students compared to fourth and sixth year students. Specialties linked to the patient obtained greater scores than those who weren't linked to the patient. Besides, 60 men (75 %) and 66 students (82.5 %) of the age group < 25 years reached adequate levels of empathy. Likewise, 32 students (50.8 %) of third year and 43 (53.8 %) of specialties linked to the patient obtained adequate levels of empathy. Conclusions: There are greater empathy scores in male students, of the age group <25 years, that are currently in third year and who chose a specialty linked to the patient, with no statistical significance found. Besides, being a man, having <25 years, being in third year and choosing specialties linked to the patient, may be a protective factor for developing adequate levels of empathy, with no confidence intervals found. (AU)

Fundamentos para la utilización de la terminología anatómica / Basis of anatomical terminology

Esta revisión apunta a dar luces sobre un problema evidente entre docentes de Anatomía Humana, profesionales y docentes clínicos. La existencia de términos anatómicos inexactos, complejos o inespecíficos, además de la existencia de Epónimos y Sinonimia, problema del cual los más perjudicados son los alumnos de pregrado en sus procesos formativos iniciales. Se darán definiciones semánticas y se situará dentro de un contexto histórico la adquisición de nuevas nomenclaturas y terminologías Anatómicas, buscando con esto justificación a la actual Terminología Anatómica la cual tiene por objetivo el desplazar la antigua Nomina Anatómica. En la parte final se entregarán ejemplos característicos de términos anatómicos, enfrentando el término antiguo con el que sugiere la actual terminología anatómica.

This revision, points to clear out the evident problem between anatomy professors, professionals and clinical professors, this is, the existence of inaccurate, complex or unspecific anatomical terms, besides the existence of eponyms and synonyms, problem of which the pre-grad students in its initial formative process are the most harmed. There will be given semantic definitions and the acquisition of new anatomic nomenclatures and terminologies will be situated within an historical context, looking with this, justification to the actual Anatomical terminology, which has for objective to displace the old Anatomical Nominee, In the final part, characteristic anatomical terms examples will be given, facing the old term with the one the actual anatomical terminology suggest.