Detection of therapeutic targets in human highly prevalent diseases through mathematical modelling of their molecular basis

Las enfermedades se producen por un mal funcionamiento del organismo. Con el fin de comprender los mecanismos de las enfermedades se debe tener en cuenta la complejidad de los organismos biológicos, no sólo como el conjunto de interacciones moleculares, sino también su dinámica. Las enfermedades se producen por un desequilibrio en la dinámica del sistema, ello implica que hacen falta métodos que permitan inducir la dinámica a partir de la red de interacciones de forma que sea posible encontrar nuevas estrategias para el tratamiento de las enfermedades. El enfoque que se ocupa de este inferir la dinámica a partir de las redes de interacciones es la biología de sistemas; esta hace uso de metodologías de modelización matemática para hacer frente a la complejidad estructural y dinámica de los organismos biológicos. En primer lugar se resumen y analizan las cuestiones generales sobre modelización matemática en biociencias, luego se presenta una revisión de aproximaciones mediante modelización matemática en el tema de infección por malaria dentro del hospedador. Cuatro enfermedades altamente prevalentes son evaluados bajo este enfoque desentrañando la complejidad molecular y celular que explica su fisiología. La malaria es altamente prevalente en los países en desarrollo, y es producida por la interacción dinámica del parásito y las células del sistema inmunológico en el torrente sanguíneo; la infección por VIH es producida en primer lugar por la invasión de los linfocitos T4 por el virus, este proceso está promovido por muchas rutas de señalización molecular desencadenadas por el virus en el interior del linfocito, que culminan con la apertura de un poro por el cual entra el VIH; la enfermedad de Alzheimer es una patología neurodegenerativa sin causa conocida, la hipótesis principal alude a la producción de un péptido neurotóxico, el β-amiloide, en ciertos dominios lipídicos formados por el movimiento lateral diferencial de los lípidos en la membrana de las neuronas; por último, el melanoma es un tipo de cáncer de melanocitos muy agresivo. Inicialmente, un microtumor crece en el torrente sanguíneo interactuando con el sistema inmune; la evolución de la enfermedad depende de esta interacción dinámica. En cada caso se proponen potenciales dianas terapéuticas en las que puede centrarse la búsqueda de nuevos fármacos contra estas enfermedades haciendo uso de los modelos que reproducen la enfermedad en determinadas condiciones

Pneumo-gaming: Computer game based on multi-level mathematical modelling and simulation used to investigate early-phase bacterial lung infection

Pneumococcal infection is the most frequent cause of pneumonia, and one of the most prevalent and dangerous diseases. The risk groups for the disease namely, infants elderly and immunosuppressed people, are more exposed and vulnerable because vaccines are not efficient in them, and when the symptoms appear the risk of death is high. Instead, preventing the alveolar infection would be a promising strategy in this group. A multilevel mathematical model converted into a game is proposed to understand the biological mechanism of the prevention of the disease through the gaming experience of the users

Co-evaluation in a problem solving practice in a bioscience subject

La co-evaluación o evaluación entre pares es reconocida como una actividad que estimula el papel activo del alumnado en el proceso de aprendizaje. Los estudiantes tienen la oportunidad de revisar el trabajo de su compañeros de clase frente a su propia evaluación lo que permite una reflexión sobre su proceso de aprendizaje. Como resultado, son capaces de reorientar sus propias estrategias de apredizaje. En esta comunicación se muestran los resultados de un ejercicio de co-evaluación llevado a cabo con un grupo de 90 estudiantes del Grado en Biología de la Universidad de La Laguna en el marco de un un curso general de Bioquímica con contenidos en cinética enzimática. Aunque ninguno realizó antes co-evaluaciones, los resultados muestran que las correcciones realizadas fueron correctas y consistentes con las de los profesoresCo-evaluation or evaluation between peers is gaining ground as a drive for the active role of the student in the learning process. Students are given the opportunity to review their classmate’s work, facing their own evaluation and thus reflecting of their learning process. As a result they are able to reorient their own strategy. In this communication we show the results of a co-evaluation exercise carried out with a group of 90 students of a degree in Biology, within a general course of biochemistry containing enzymology issues. Although none of them have done co-evaluations before, results show that the corrections made were refined and consistent with those made by teacher

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Recursos audiovisuales para la bioquímica básica

Estos vídeos forman parte del material docente para la asignatura de bioquímica básica de diversos Grados universitarios de la Universidad de La Laguna sobre el cual trabajar en el formato de docencia invertida. El material fue creado y aplicado dentro del contexto de un Proyecto de Innovación y Transferencia Educativa de la Universidad de La Laguna para los cursos 2021-22 y 2022-23 titulado: "LA IMPLEMENTACIÓN DEL PUZZLE DE ARONSON COMO METODOLOGÍA DE ENSEÑANZA-APRENDIZAJE ACTIVA Y CENTRADA EN EL ESTUDIANTE EN LA RAMA DE BIOLOGÍA CELULAR Y MOLECULAR".</p

SIMENZKIN biochemistry seminar.xlsx

SIMENZKIN is a data table file (Excel and ods) programmed to simulate enzymatic metabolic reactions using the Michaelis-Menten formalism. Is optimized for being used in a practical module for a enzymology class together with the problem attached