Design and synthesis of new molecules based on indolium derivatives for two-photon absorption bioimaging applications

Bioimaging is the visualization of biological processes in real time, interfering as less as possible with these and using non-invasive methods. Among others, fluorescence methods have acquired a very important role in these purposes through the nature of the light. Bioimaging pretends to understand how our organism works identifing subcellular organelles, following cellular processes, quantifying ion or biological species and visualising interactions of molecules with their targets in living cells or tissues. In the last decades, two-photon (TP) microscopy is unseating classical one-photon (OP) microscopy due to its advantages, such as the use of lower energy excitation wavelengths or the possibility of focus in depth, among others. Nowadays, it is an interesting target design and develop of new probes for TP microscopy to biomaging. Fluorophores based on indolenines are a family of compounds with promising properties in this sense. In this work, we present the design, synthesis and characterization of new indolium derivatives with promising properties to be used in bioimaging applications in living cells with different purposes.Real Sociedad Española de Química, Jóvenes Invetigadores Químicos, Facultad de Ciencias Ambientales y Bioquímica (UCLM), Merck, Cortes de Castilla la Mancha, Reaxys (Elsevier), Diputación de Toledo, MestreLab Research, Sección Territorial de Castilla la Mancha (RSEQ), Grupo especializado en Nanociencia y Materiales Moleculares (RESEQ), Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

New molecules based indolium for two-photon absortion bioimaging applications

The development of organic materials with 2PA has attracted intensive attention in the past two decades. In two-photon bio-imaging applications the design of the chromophore requires to have a good cross-section and good biological compatibility which depends on the molecular volume and polarity. Fluorophores based on indolenines are one of these organic materials. These compounds and related are used in fluorescence microscopy as in super-resolution. The non-invasive nature of light allows imaging of biological specimens with minimal disruption, so you can see the dynamic processes that occur in living cells and tissues. In this work, we present the design, synthesis and characterization of new indolium derivatives. These compounds are easy to achieve with good yields and good photophysical properties. In addition, time-dependent density functional theory (TDDFT) has been carried out to investigate the energy level of the ground and excited state. Also, these molecules have been proved on cells.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Tuning pKa in new molecules based on indolines for two-photon absorption bioimaging applications

Fluorescence-based biosensors have become essential tools for modern biology, allowing real-time monitoring of biological processes within living cells. The differences between pH play a significant role in multiple biological process such as proliferation, apoptosis, endocytic process and defense. Therefore, intracellular fluorescent pH probes comprise one of the most widely used families of biosensors in microscopy. In this work, we present the design, synthesis and characterization of new one and two photon pH activatable fluorescent probes based on naphthalene-indoline derivatives with an off-on response to different pH environments. These compounds are easy to achieve with good yields and have good photophysical properties. Simple modifications in the structure of these compounds allow tuning their pKa easily and cover a width range of pH in their applications. The preliminary results obtained with these fluorescent probes indicate that they have promising properties to be use in bioimaging applications in living cells.Real Sociedad Española de Química y Grupo Especializado de Química Orgánica de la RSEQ•Universidade de Santiago de Compostela • CIQUS • Lilly • Mestrelab Research •Thieme •Scharlab • Acros • ABCR • AMSLab • GalChimia • Elsevier • The Journal of the American Chemical Society • ACS Omega • Organic Letters • The Journal of Organic Chemistry • Accounts of Chemical Research. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Mobile application to travel the world using virtual reality and machine learning

This research intends to make travel and culture an accessible possibility for all. With a phone and a VRHeadset, people will have the opportunity to see some of the most amazing scenes in the world and learn about the history and culture of famous landmarks without leaving the comfort of their own homes

Use of Epidemiological and Geostatistical Methods to Understand the Epidemic of Homicides in Baltimore, 2005 to 2017

Violence is widely recognized as a public health problem. Baltimore, Maryland, a city 45 miles north of Washington, DC, has experienced homicide rates several times higher than those experienced by the United States as a country since at least 1975. Since 2015, Baltimore City has experienced an epidemic of homicides, with an average homicide rate of over 50 homicides per 100,000 residents. We analyzed the individual social characteristics of the victims of homicide in Baltimore City between 2005 and 2017. We used descriptive epidemiology to understand the distribution of social risk factors for victimization in individuals. We also used information on the location of homicides in this time period — along with socioeconomic information on Community Statistical Areas (CSA) — to understand the association between neighborhood environmental characteristics and the homicide rates in those CSAs. We finally took inventory of violence prevention programs existing in Baltimore City as of 2017, and we compared the goals of those programs with the findings from the analysis of victims and the victim location. Through the use of epidemiological and geostatistical methods, we found that not all segments of the population of Baltimore City experienced the same levels of homicide victimization. African American men between the ages of 15 and 34 made up over 61% of the homicide victims between 2005 and 2017 in Baltimore City. Most of the homicides showed spatial clustering around CSAs with elevated levels of poverty and disorder (e.g. broken street lights). Hot spot analysis using person, place, and time showed that hot spots tended to appear or disappear depending on the year of the homicides. The government and civil society in Baltimore City are working in different ways to address violence. Existing programs would do well to expand into the emerging hot spots of homicides, while other programs would probably have a greater impact on violence if they combined efforts and focused on a specific segment of the population. Finally, there is a great opportunity for healthcare providers to treat violence with the same approaches as other public health problems

New indolium fluorofores for two-photon absortion (2PA) bioimaging applications

The development of organic materials with 2PA has attracted intensive attention in the past two decades [1]. In two-photon bio-imaging applications the design of the chromophore requires to have a good cross-section (σ2PA) and good biological compatibility which depends on the molecular volume and polarity [2]. In this work, we present the design, synthesis and characterization of new indolium derivatives. These compounds are easy to achieve with good yields and good photophysical properties. In addition, time-dependent density functional theory (TDDFT) has been carried out to investigate the energy level of the ground and excited state. Their spectral properties and assays performed on cultured cells, demonstrate the potential of these compounds as fluorescent probes with application in two-photon bio-imaging.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Ministerio de Ciencia e Innovación-Spain (CTQ2013-41339-P and CTQ2015- 71896-REDT

Detecting hydroxyl radical with a new two-photon fluorescent probe in living cells

Reactive oxygen species (ROS) are known to be involved in the onset and development of multiple diseases, including cancer, cardiovascular diseases, neurodegenerative diseases and diabetes among others. Generation of ROS is a phenomenon that results from normal cell metabolism as well as from the response to certain pathologic stimuli like certain cytokines, xenobiotics and bacterial infection. These ROS are highly reactive, short-lived molecules that play critical roles in the living cell and it is well accepted that cellular oxidative stress results from the imbalance between generation and elimination of ROS in cells. In this work, we describe the design and synthesis of a two photon (TP) organelle-targeting activatable fluorescent probe. This probe is a naphthalene-indoline compound that targets specifically lysosomes, reaching these organelles in the fluorescence “off” state and minimizing background reactions. Upon arrival at the lysosomes, the probe is triggered and a fluorescence “on” signal is observed that can be combined with TP microscopy to image the lysosomal •OH in living cells.Real Sociedad Española de Química y Grupo Especializado de Química Orgánica de la RSEQ•Universidade de Santiago de Compostela • CIQUS • Lilly • Mestrelab Research •Thieme •Scharlab • Acros • ABCR • AMSLab • GalChimia • Elsevier • The Journal of the American Chemical Society • ACS Omega • Organic Letters • The Journal of Organic Chemistry • Accounts of Chemical Research. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Synthesis of fluorescent dendrimeric antigen efficiently internalized by human dendritic cells

A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups has been synthetized. The synthesis implies a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD).[1] The introduction of a cystamine core allows the incorporation of this dendrons into a 1,8-naphthalimide fluorofore functionalized with a maleimide group. The fluorescence properties of this DeAn has been studied and compared with the properties of an equivalent dendron possessing amino-terminal groups. This DeAn has been used as a synthetic antigen in a biomedical assay that tests the amoxicillin sensitivity of dendritic cells (DC) from tolerant and allergic patients.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

cdcatR: An R package for cognitive diagnostic computerized adaptive testing

Cognitive diagnosis models (CDMs) are confirmatory latent class models that provide fine-grained information about skills and cognitive processes. These models have gained attention in the last few years because of their usefulness in educational and psychological settings. Recently, numerous developments have been made to allow for the implementation of cognitive diagnosis computerized adaptive testing (CD-CAT). Despite methodological advances, CD-CAT applications are still scarce. To facilitate research and the emergence of empirical applications in this area, we have developed the cdcatR package for R software. The purpose of this document is to illustrate the different functions included in this package. The package includes functionalities for data generation, model selection based on relative fit information, implementation of several item selection rules (including item exposure control), and CD-CAT performance evaluation in terms of classification accuracy, item exposure, and test length. In conclusion, an R package is made available to researchers and practitioners that allows for an easy implementation of CD-CAT in both simulation and applied studies. Ultimately, this is expected to facilitate the development of empirical applications in this areaThis research was funded by Ministerio de Ciencia e Innovación, grant number PSI2017- 85022-P, and Cátedra de Modelos y Aplicaciones Psicométricas (Instituto de Ingeniería del Conocimiento and Autonomous University of Madrid

Synthesis of fluorescent BAPAD dendrimeric structrures for biomedical applications

Comunicación oral presentada en el Congreso IV Encuentro sobre Dendrímeros, Santiago de Compostela, 2014In this work, we present the synthesis and characterization of BAPAD1 fluorescent Dendrimeric-Antigens (DeAn), to study the dendritic cell maturation as a test to detect drug allergy reactions. Recently our research group developed a new kind of dendrimer, called BAPAD1, that we have used in this work to obtain the dendrimeric moiety of the target molecule. To this avail we synthesized a generation two BAPAD dendrimer using cystamine as core. Then, the free amine groups on the surface of the dendrimer were functionalized with an amoxiciloyl group (AXO), the allergenic determinant to the beta-lactam antibiotic amoxicillin. By the reduction of the disulfur bond we obtained two dendrons with a thiol group in the focal point, useful to attach a fluorescent probe. We synthesize as fluorescent moiety a naphthalimide derivative with a maleimide group upon which the thiol group of the dendron is added by a click reaction.2 In this way we obtained the target molecule to be used in the basophil activation test. The fluorescent DeAn (F-DeAn) has been fully characterized by NMR and MS techniques, and their fluorescent properties well established in aqueous biological media. The fluorescent dendron without the haptenic moieties at the periphery has been also obtained and fully characterized as a control assay. Both molecules have been also characterized using molecular dynamics simulation calculations. We show also here how these dendrimeric structures interact with dendritic cells and are internalized by them.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec