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CHANGING THE PARADIGM OF THE ECOTOXICITY ASSAYS APPLIED IN ENVIRONMENTAL RISK ASSESSMENT: FROM TOXICITY TO HABITAT SELECTION

CHANGING THE PARADIGM OF THE ECOTOXICITY ASSAYS APPLIED IN ENVIRONMENTAL RISK ASSESSMENT: FROM TOXICITY TO HABITAT SELECTION


N THE ENVIRONMENTAL RISK ASSESSMENT SCHEMES, ECOTOXICOLOGICAL ASSAYS HAVE BEEN CONSIDERED AN INDISPENSABLE TOOL TO ASSESS THE TOXICITY CAUSED BY THE CONTAMINANTS ON ORGANISMS. ALTHOUGH BIOASSAYS TRY TO SIMULATE THE ENVIRONMENTAL CONDITIONS AT WHICH ORGANISMS ARE REALLY EXPOSED, THE EXPERIMENTAL ENVIRONMENT SIMULATED IN THE BIOASSAYS IS VERY REDUCTIONIST IF COMPARED TO A REAL SYSTEM: FOR INSTANCE, THE FORCED EXPOSURE USED TO ASSESS THE TOXICITY OF THE CHEMICAL COMPOUNDS. TRADITIONALLY, BIOASSAYS ARE PERFORMED IN A CONFINED ENVIRONMENT, WHERE ORGANISMS ARE FORCEDLY EXPOSED TO THE CONTAMINANTS AND THE EFFECTS ARE MEASURED AFTER AN EXPOSURE PERIOD. THIS FORCED EXPOSURE COULD, BE CONSIDERED ENVIRONMENTALLY UNREALISTIC AS IT: (I) ASSUMES THAT ORGANISMS ARE PASSIVE AGENTS ACCEPTING THE CONTINUOUS EXPOSURE TO CONTAMINANTS, (II) IGNORES THAT ORGANISMS CAN DETECT AND AVOID CONTAMINATION BY ESCAPING TOWARDS LESS CONTAMINATED AREAS AND (III) DOES NOT TAKE INTO ACCOUNT IF AND HOW CONTAMINANTS DETERMINE THE DISPLACEMENT OF ORGANISMS AND THEIR HABITAT SELECTION PROCESSES. THE PRESENT PROJECT WILL PROVIDE A NOVEL APPROACH TO BIOASSAYS, BY USING A NON-FORCED EXPOSURE SYSTEM, TO SIMULATE THE DISPERSION PATTERN OF CONTAMINANTS, THROUGH WHICH ORGANISMS CAN FREELY MOVE AND SELECT AREAS WITH DIFFERENT CONTAMINATION LEVELS. THIS AVOIDANCE RESPONSE PREVENTS ORGANISMS OF SUFFERING TOXIC EFFECTS CAUSED BY THE CONTINUOUS EXPOSURE AND IT FOCUSES ON THE EFFECTS RELATED TO THEIR SPATIAL DISTRIBUTION. THE NON-FORCED APPROACH ALLOWS FOR REDUCING THE LIMITATIONS OF THE FORCED EXPOSURE USED IN THE TRADITIONAL BIOASSAYS AND IT BREAKS THE WIDELY ACCEPTED PARADIGM THAT THE RISK OF A CHEMICAL COMPOUND IS CONDITIONED TO THE TOXICITY CAUSED AT THE INDIVIDUAL LEVEL. THE GOAL OF THE PRESENT PROJECT IS TO DEVELOP AND IMPLEMENT A NON-FORCED EXPOSURE SYSTEM TO BE USED IN ENVIRONMENTAL RISK STUDIES AND, MOREOVER, TO ASSESS HOW THIS APPROACH CAN HELP PREDICTING THE ROLE OF CONTAMINANTS IN HABITAT SELECTION.

ROLE OF EXTRACELLULAR POLYMERIC SUBSTANCES (EPS) IN MINERAL PRECIPITATION IN THE OCEAN: IMPLICATION FOR BIOGEOCHEMICAL CYCLES.

ROLE OF EXTRACELLULAR POLYMERIC SUBSTANCES (EPS) IN MINERAL PRECIPITATION IN THE OCEAN: IMPLICATION FOR BIOGEOCHEMICAL CYCLES.


THIS PROJECT AIMS A MULTIDISCIPLINARY RESEARCH OF THE ROLE THAT EXTRACELLULAR POLYMERIC SUBSTANCES (EPS) PLAY IN MINERAL PRECIPITATION IN THE OCEANS AND IN TURN IN BIOGEOCHEMICAL CYCLES NOT FULLY UNDERSTOOD. MECHANISMS FOR MINERAL PRECIPITATION IN THE OCEAN ARE NOT KNOWN YET FOR CERTAIN MINERALS. AS EXAMPLE, THE BARITE PRECIPITATION AND THE BIOGEOCHEMICAL CYCLE OF BARIUM, OF KEY IMPORTANCE IN GLOBAL CHANGE RESEARCH BECAUSE IT IS CLOSELY RELATED TO THE CARBON CYCLE, ARE VERY POORLY UNDERSTOOD. THIS MINERAL, BARITE, IS A RELIABLE PRODUCTIVITY PROXY SINCE BA DISTRIBUTION IN THE OCEAN WATER COLUMN AND SEDIMENTS MIRRORS CARBON FLUXES. HOWEVER, DESPITE BA PROXIES HAVE USED FOR DECADES, BA PRECIPITATION IN UNDERSATURATED SEAWATER IS NOT YET KNOWN. OUR RECENT FINDINGS DEMONSTRATE THAT EPS PLAY A MAJOR ROLE, WHICH HAS OPENED AN EXCITING FIELD OF RESEARCH IN ORDER TO EXPLORE THE ROLE OF EPS IN THE SEDIMENTARY RECORD. SIMILARLY OTHER MINERALS HAVE BEEN TRADITIONALLY ATTRIBUTED INORGANIC PRECIPITATION AS IS THE CASE FOR CLAYS. HOWEVER, EPS MAY PLAY AN ESSENTIAL ROLE Y CLAY PRECIPITATION, WHICH IN TURN HAS MAJOR IMPORTANCE IN OIL RESERVOIRS WHERE CLAY FORMATION MAY SIGNIFICANTLY ALTER ORIGINAL POROSITY. THUS, WE PROPOSE TO INVESTIGATE THE ROLE OF EPS IN MINERAL PRECIPITATION AND ELEMENT ABSORPTION IN THE OCEAN AS WELL AS IN BIOGEOCHEMICAL CYCLES. THE RESEARCH TEAM IS HIGHLY MULTIDISCIPLINARY INVOLVING EXPERTISE ON MICROBIOLOGY, MINERALOGY, GEOCHEMISTRY, CRYSTALLOGRAPHY, SEDIMENTOLOGY AND GEOMICROBIOLOGY, AS THE PROPOSED RESEARCH REQUIRES A MULTIPROXY APPROACH.

ANIMAL PERSONALITY AND GUT MICROBIOME

ANIMAL PERSONALITY AND GUT MICROBIOME


ANIMAL PERSONALITIES, OR CONSISTENT AMONG-INDIVIDUAL DIFFERENCES IN BEHAVIOR, ARE UBIQUITOUS ACROSS TAXA, YET THE MECHANISMS OF ITS ESTABLISHMENT ARE POORLY UNDERSTOOD. UNDERSTANDING THE MECHANISMS OF ANIMAL PERSONALITY FORMATION WOULD THEREFORE SHED LIGHT ON MANY POORLY UNDERSTOOD PROCESSES OF ECOSYSTEMS FUNCTIONING. HERE, WE HYPOTHESIZE THAT GUT MICROBIOME COMPOSITION AND ITS ACTIVITY CAN PREDICT INDIVIDUAL DIFFERENCES IN ANIMAL BEHAVIOR. WE HYPOTHESIZE THAT THE HOST BEHAVIOR - GUT MICROBIOTA CONNECTION IS MECHANISTICALLY EXPLAINED BY THE COMBINATION OF THE MICROBIAL SPECIES COMPOSITION AND THEIR SPECIFIC METABOLIC ACTIVITY. PROKARYOTES RELEASE METABOLITES IN THE GUT LUMEN THAT COULD INFLUENCE ANIMAL PERSONALITY. TO TEST OUR HYPOTHESIS, WE WILL COMBINE THE STANDARDIZED LABORATORY ASSAYS TO TEST ANIMAL PERSONALITY WITH THE MICROBIAL CULTURE-INDEPENDENT APPROACHES TO CHARACTERIZE THE STRUCTURE (METAGENOMICS), FUNCTION (METAPROTEOMICS) AND METABOLITE PRODUCTION (METABOLOMICS) OF MICROBIAL GUT COMMUNITIES. THE MODEL ANIMAL CONSIDERED TO TEST OUR HYPOTHESIS WILL BE A TELEOST FISH SPECIES, TAKING THE ADVANTAGES OF THE NATURAL GENETIC VARIATIONS FOUND IN FISH POPULATIONS AND THE EXISTENCE OF HIGHLY STANDARDIZED PERSONALITY TESTS FOR THESE ANIMALS. WE WILL CONSIDER TWO TYPES OF POPULATIONS; WILD-CAUGHT AND LABORATORY-REARED INDIVIDUALS. IF OUR WORKING HYPOTHESIS RECEIVES EMPIRICAL SUPPORT, OUR WORK WILL OPEN A NEW FRONTIER TO THE UNDERSTANDING OF THE ORIGINS OF ANIMAL BEHAVIOR AND ITS IMPLICATIONS IN MANY ECOLOGICAL AND EVOLUTIONARY PROCESSES, WHICH ULTIMATELY MAY DEPEND ON THE ANIMAL PERSONALITIES. IN ADDITION, OUR WORK WILL NOT ONLY PRODUCE FUNDAMENTAL KNOWLEDGE THAT COULD SUPPLEMENT THE UNDERSTANDING IN HOW GUT MICROBIOMES COULD IMPACT A VARIETY OF STRESS-RELATED BEHAVIORS LIKE ANXIETY AND DEPRESSION IN HUMAN, BUT ALSO ON SOME PRACTICAL ASPECTS IN AQUACULTURE RELATED TO FEED FORMULATION AND BEHAVIORAL RESPONSES

EXTRAORDINARY OPTICAL TRANSMISSION IN SOLAR CELLS

EXTRAORDINARY OPTICAL TRANSMISSION IN SOLAR CELLS


HERE WE PROPOSE THAT PROPERLY DESIGNED NANOWIRES AT THE INTERFACE BETWEEN TWO MATERIALS OF DIFFERING REFRACTIVE INDEX CREATE NEGLIGIBLE SHADOWING. MOST OPTOELECTRONIC DEVICES, SUCH AS SOLAR CELLS AND LIGHT EMITTING DIODES (LEDS), NEED ELECTRICAL CONTACTS ON THE TOP SURFACE OF THE DEVICE, BUT THESE CAUSE LIGHT REFLECTION AND ABSORPTION LOSSES. SO FAR THIS HAS BEEN VIEWED AS AN UNAVOIDABLE COMPROMISE LIMITING THE OVERALL ENERGY CONVERSION EFFICIENCY OF OPTOELECTRONIC DEVICES. INSTEAD WE PROPOSE THAT METALS CAN BE MADE, FOR MANY PRACTICAL PURPOSES, FULLY TRANSPARENT. OUR PRELIMINARY RESULTS SUGGEST THAT IT IS POSSIBLE TO HAVE ZERO, AND EVEN NEGATIVE EFFECTIVE SHADOW FACTORS, AND WE PROPOSE TO EXPERIMENTALLY DEMONSTRATE NANOSTRUCTURED TOP CONTACTS WITH NEAR ZERO SHADOW FACTORS IN A BROADBAND WAVELENGTH RANGE. THIS PROPOSAL MIGHT ENABLE A NEW GENERATION OF HIGHLY EFFICIENT SOLAR CELLS AND LIGHT EMITTING DIODES.

NOVEL ELECTRODES FOR NA-ION BATTERIES BASED ON THE NA-CL-NI-CU-O-C SYSTEM

NOVEL ELECTRODES FOR NA-ION BATTERIES BASED ON THE NA-CL-NI-CU-O-C SYSTEM


THE ENERGY STORAGE USING BATTERIES HAS BECOME A PRIORITY ISSUE, AND ONE OF THE MOST IMPORTANT RESEARCH LINES IS THE SEARCH FOR NEW MATERIALS FOR ELECTRODES IN NA-ION BATTERIES. THE PROPOSAL IS BASED ON AN ANOMALOUS RESULT OBTAINED RECENTLY DURING THE EVALUATION OF THIN LAYERS OF NIO ON COPPER AS A POSSIBLE ELECTRODE FOR NA-ION BATTERIES. THE USUAL MAXIMUM DISCHARGE CAPACITY DURING THE FIRST CHARGE-DISCHARGE CYCLES IS 400 MAHG-1, A VALUE THAT GRADUALLY DECREASES WITH THE NUMBER OF CYCLES. HOWEVER, IN THIS ANOMALOUS CASE, THE CYCLING BEHAVIOR WAS RADICALLY DIFFERENT, SINCE THERE IS A CONTINUOUS INCREASE IN THE CHARGE AND DISCHARGE CAPACITIES, REACHING VALUES AS HIGH AS 9300 MAHG-1 AT THE END OF THE CYCLING. THIS BEHAVIOR IS RELATED TO THE INTERACTION BETWEEN MATERIALS, AND THE FORMATION OF A NEW MATERIAL. THE FINAL GOAL OF THE PROPOSAL IS TO SYNTHESIZE THIS NEW MATERIAL THROUGH SEVERAL SPECIFIC OBJECTIVES: MODELING AND THERMODYNAMIC CALCULATION OF THE REACTIONS INVLOVED, PROCESSING OF THE NEW MATERIAL FROM COMMERCIAL PRODUCTS (NIO, CU, NA, SODIUM SALTS, ETC.) BASED ON THE RESULTS OF THE THERMODYNAMIC STUDY, AND OPTIMIZATION OF THE SYNTHESIS CONDITIONS CONSIDERING THE REACTION ATMOSPHERE, VOLTAGE AND CURRENT, PHYSICAL-CHEMICAL CHARACTERIZATION OF THE NEW MATERIAL BOTH FROM THE CHEMICAL COMPOSITION AND STRUCTURAL POINT OF VIEW, AND ELECTROCHEMICAL CHARACTERIZATION AS AN ELECTRODE FOR NA-ION BATTERIES. THE MOST IMPORTANT POINT OF THIS PROPOSAL IS THE FEASIBLE POSSIBILITY OF SYNTHESIZING THIS NEW MATERIAL WITH EXCELLENT PROPERTIES AS AN ELECTRODE FOR NA-ION BATTERIES, REACHING CAPACITY VALUES OF AT LEAST 10 TIMES THE CURRENT VALUES. IN ADDITION TO THIS HIGH SCIENTIFIC IMPACT, THIS MULTIDISCIPLINARY WORK WOULD BRING SOCIAL AND ECONOMIC ADVANTAGES IN THE DEVELOPMENT OF NEW LI-FREE BATTERIES AND REDUCTION OF FOSSIL FUEL CONSUMPTION.

EXPLORING 2D MATERIALS FOR DEVELOPING KINETIC INDUCTANCE DETECTORS

EXPLORING 2D MATERIALS FOR DEVELOPING KINETIC INDUCTANCE DETECTORS


FUTURE SPACE SCIENCE MISSIONS AND INSTRUMENTATION IN GROUND BASED ARE, SO FAR, LIMITED BY THE AVAILABILITY OF HIGH SENTITVITY IMAGING DETECTOR ARRAY TECHNOLOGY FOR THE MM-FIR WAVELENGTH RANGE (3 MM TO 30 and 956;M). SUPERCONDUCTING KINETIC INDUCTANCE DETECTORS (KIDS) WERE PROPOSED, A DECADE AGO, TO PROVIDE LARGE FORMAT CAMERA DUE TO ITS INTRINSIC POSSIBILITY OF MULTIPLEXING IN THE FREQUENCY DOMAIN, ALLOWING THOUSANDS OF PIXELS TO BE READ OUT THROUGH A SINGLE CABLE. HOWEVER, THESE DETECTORS HAVE ALREADY DEMONSTRATED VERY LOW OPTICAL EFFICIENCY IN LOW BACKGROUND IN THE THZ RANGE AND, IN ADDITION, THEY OPERATE AT EXTREMELY LOW TEMPERATURE (FEW MK). AS A RESULT, AN ALTERNATIVE IS NECESSARY TO PROVIDE THE REQUIRED LARGE ARRAY DETECTOR OPERANTING IN THE THZ RANGE WITH SENSITIVITIES MATCHING THAT REQUIRED FOR FUTURE SPACE MISSIONS WITH LARGE CRYOGENIC TELESCOPES (4-6 K). IN THIS PROJECT, WE PROPOSE TO FOLLOW THE RECENTLY CLAIMED DETECTION OF A CHANGE OF KINETIC INDUCTANCE ON GRAPHENE WITH THE APPLIED VOLTAGE GATE EXPLORE THE POSIBILITY TO USE 2D MATERIALS FOR THE DEVELOPMENT OF A NEW GENERATION OF STATE-OF-THE-ART KINETIC INDUCTANCE DETECTOR FOR ASTRONOMICAL OBSERVATIONS IN THE FAR-IR. THIS TYPE OF 2D DETECTORS HAVE THE POTENTIAL TO OPEN A UNIQUE POSSIBILITY FOR SPACE OBSERVATORIES TO OPERATE WITH THE ULTIMATE SENSITIVITY, ONLY LIMITED BY THE LOW BACKGOUND PROVIDED BY CRIOGENIC TELESCOPES, KEEPING THE INTRISIC MULTIPLEXING CAPABILITY (LARGE CAMERAS) WITH THE ADVANTAGE TO OPERATE AT HIGHER TEMPERATURES ( 30K) THAN THE MOST SENSITIVE DETECTOR USED NOWADAYS (TENS OF MK). IN ADDITION, THIS TYPE OF NEW DETECTORS WILL BE USED IN A WIDE RANGE OF APPLICATIONS.

VERIFICATION OF THE EXISTENCE OF MACROSCALE REPULSIVE CASIMIR FORCES IN SUSPENDED SELF-STANDING FILMS.

VERIFICATION OF THE EXISTENCE OF MACROSCALE REPULSIVE CASIMIR FORCES IN SUSPENDED SELF-STANDING FILMS.


THE ULTIMATE GOAL OF THE VERSUS PROJECT IS THE FIRST OBSERVATION OF REPULSIVE CASIMIR-LIFSHITZ FORCES IN MACROSCOPIC PLANE-PARALLEL SYSTEMS. TO THIS END, IT WILL FOCUS ON THE DESIGN, FABRICATION, AND CHARACTERIZATION OF OPTICAL MATERIALS THAT ALLOW CONTROLLING THE INTENSITY AND NATURE OF THE CASIMIR-LIFSHITZ FORCE, SO THAT LEVITATION PHENOMENA CAN BE OBSERVED AND CHARACTERIZED DUE TO THE BALANCE BETWEEN THE LATTER AND GRAVITY FORCE. THIS RADICALLY NEW APPROACH MAKES USE OF OPTICAL SPECTROSCOPIC TECHNIQUES (BASED ON OPTICAL INTERFEROMETRY BETWEEN THE PARTIALLY REFLECTED AND TRANSMITTED LIGHT AT THE INTERFACES OF THE PLANE-PARALLEL SYSTEM) FOR CHARACTERIZING THE EQUILIBRIUM DISTANCE AT WHICH THE SYSTEM LEVITATES OVER A SUBSTRATE. ACCORDING TO VERY RECENT RESULTS ATTAINED BY THE APPLICANT GROUP, IT IS POSSIBLE TO FIND MATERIALS WHOSE OPTICAL CONSTANTS AND DENSITIES ARE SUCH THAT WHEN THEY ARE IMMERSED IN A FLUID THEY CAN LEVITATE OVER A SUBSTRATE AS A RESULT OF THE AFOREMENTIONED FORCE BALANCE. OUR GROUP HAS RECENTLY DEMONSTRATED THEORETICALLY THAT THERE IS A NUMBER OF MATERIALS THAT PREPARED IN THIN FILMS (< 1 MICROMETER) CAN LEVITATE SEVERAL TENS OR HUNDREDS OF NANOMETERS OVER A CAREFULLY SELECTED SUBSTRATE. SPECIFICALLY, THIN LAYERS MADE OF TEFLON, POLYSTYRENE OR SILICON DIOXIDE IMMERSED IN GLYCEROL ARE EXPECTED TO LEVITATE OVER A SILICON WAFER, BEING POSSIBLE TO TUNE THE EQUILIBRIUM DISTANCES AT WHICH SUCH LAYERS WILL BE SUSPENDED THROUGH THEIR THICKNESSES AND TEMPERATURE OF THE SYSTEM. THE DEVISED SELF-STANDING THIN FILMS (IN SINGLE LAYERS OR MULTILAYER ARRANGEMENTS) MUST BE COMPACT, MECHANICALLY STABLE, OF SMOOTH SURFACES, OF CONTROLLED THICKNESS, AND CHEMICALLY COMPATIBLE WITH THE FLUID IN WHICH THEY ARE IMMERSED. THE MACROSCOPIC OBSERVATION OF REPULSIVE CASIMIR-LIFSHITZ FORCES, NEVER REPORTED BEFORE, THROUGH OPTICAL SPECTROSCOPIC MEASUREMENTS WOULD CONSTITUTE AN UNPRECEDENTED MILESTONE IN THE FIELD OF FUNDAMENTAL MATTER INTERACTIONS.

WIRELESS INDUCTION OF ELECTRIC FIELDS FOR THE GENERATION OF A COUPLED BATTERY/CAPACITOR FLOW CELL

WIRELESS INDUCTION OF ELECTRIC FIELDS FOR THE GENERATION OF A COUPLED BATTERY/CAPACITOR FLOW CELL


OUR PROJECT PRESENTS A DEVICE BASED ON A REDOX FLOW CELL USING SEMI-SOLID ELECTRODES THAT OBVIATES THE NEED OF AN ION-SELECTIVE MEMBRANE. WE PROPOSE A COMPLETELY DIFFERENT CELL DESIGN THAT AVOIDS ITS NEED BY REVERTING THE REQUIREMENTS FOR ELECTRON AND ION CONDUCTORSAT THE PLACE OF THE ION-CONDUCTING MEMBRANE WE USE AN ELECTRON-CONDUCTING PLATE THAT BLOCKS ION FLOW. AT BOTH SIDES WE PLACE TWO FLOWABLE ELECTRODES. THE TWO DIFFERENT REDOX COUPLES ARE ELECTRONICALLY IN CONTACT THROUGH THE MIDDLE OF THE CELL, BUT AT OPEN CIRCUIT REACTIONS CANNOT PROCEED BECAUSE OF CHARGE ACCUMULATION AT BOTH SIDES, THAT CHARGES THE ELECTRODE-ELECTROLYTE INTERFACE. TO ACCESS THESE INTERFACES WE INTRODUCE A ¿WIRELESS¿ CONTACT TO THE FLOWABLE ELECTRODES. THIS CONTACT IS PROVIDED BY IONS RELEASED BY A CAPACITIVE HALF-CELL, WHICH WILL BE ABLE TO NEUTRALIZE THE IONIC ACCUMULATION IN THE MIDDLE COMPARTMENTS BY AN IONIC CURRENT, WHICH IN TURN WILL CHARGE ITS INTERFACE AND SUSTAIN AN ELECTRONIC CURRENT. THE CAPACITIVE HALF-CELLS MAY BE SEEN AS IONIC TO ELECTRONIC CURRENT TRANSLATORS. THE OVERALL DEVICE WILL THEN CONSIST OF TWO EXTERNAL CAPACITIVE HALF-CELLS SEPARATED BY THE TWO BATTERY HALF CELLS. THE COUPLED CAPACITIVE PART WILL BE A SEMI SOLID FLOWABLE CAPACITOR. THE COUPLING OF THE LOW-RATE BATTERY HALF-CELLS WITH THE CAPACITIVE PARTS EFFECTIVELY PROVIDES A BATTERY-SUPERCAPACITOR HYBRID DEVICE, ABLE TO POTENTIALLY ACHIEVE INTRINSICALLY HIGH POWER AND ENERGY. IN ADDITION, THE USE OF A DENSE SEPARATOR AVOIDS ANY MIXING BETWEEN THE ELECTROLYTES, AND MAKES POSSIBLE A COMPLETELY INDEPENDENT CHOICE OF BOTH, ANOLYTE AND CATHOLYTE. FOR A PROOF OF CONCEPT OF THIS DEVICE WE CHOSE AQUEOUS ZN/O2 AS BATTERY CHEMISTRY. THE SLUGGISH KINETICS OF METAL AIR BATTERIES WILL BE COMPENSATED BY THE CAPACITIVE COMPONENT, WHICH ALSO INFERS LONGER DURABILITY.

GENERATION OF A NOVEL VERSATILE REPORTER FOR THE IN VIVO DETECTION OF GENE EXPRESSION VARIATIONS BY POSITRON EMISSION TOMOGRAPHY (PET)

GENERATION OF A NOVEL VERSATILE REPORTER FOR THE IN VIVO DETECTION OF GENE EXPRESSION VARIATIONS BY POSITRON EMISSION TOMOGRAPHY (PET)


THIS IS A PROOF-OF-CONCEPT PROPOSAL: TO ESTABLISH WHETHER THE EXPRESSION OF A BACTERIAL B-LACTAMASE CAN BE USED AS A TOOL FOR MONITORING CHANGES IN THE LEVELS OF GENE EXPRESSION IN VIVO. THE SUCCESS OF THIS PROJECT WILL LEAD TO THE GENERATION OF TRANSGENIC ANIMALS OF GREAT VALUE IN PRECLINICAL RESEARCH. IN VIVO NONINVASIVE IMAGING IS THE TOOL OF CHOICE IN PRECLINICAL RESEARCH TO EVALUATE THE EVOLUTION OF DISEASES AND THEIR RESPONSE TO THERAPY. THE OBTAINING OF IN VIVO IMAGES OF GENES BY POSITRON EMISSION TOMOGRAPHY (PET) IS THE TECHNIQUE CHOSEN FOR THIS PURPOSE. THE CURRENT PET IRGS HAVE SEVERAL DRAWBACKS, BEING DIFFICULT TO DETERMINE TO WHAT EXTENT THE SIGNAL DETECTED IS DUE TO A TRANSCRIPTIONAL OR PHOSPHORYLATION CHANGE, INDEPENDENTLY OF THE PROMOTER ACTIVITY AND THE NON-SPECIFICITY DUE TO THE INTERACTION OF THE LABELED LIGAND WITH THE ENDOGENOUS PROTEINS. IN ADDITION, SOME OF THESE CONTROLS ARE HIGHLY IMMUNOGENIC, WHICH LIMITS THEIR USE TO IMMUNO-RESISTANT ANIMALS. TO OVERCOME THESE LIMITATIONS, WE PLAN TO DEVELOP AN IRG SYSTEM BASED ON THE EXPRESSION OF A MODIFIED FORM OF A BACTERIAL B-LACTAMASE. IT IS A MUTANT VARIANT IN THE CATALYTIC CENTER THAT BINDS IRREVERSIBLY TO B-LACTAM ANTIBIOTICS. THE AMOUNTS OF THIS B-LACTAMASE EXPRESSED FROM THE PROMOTER WILL BE QUANTIFIED BY PET, AFTER THE ADMINISTRATION OF AN AMPICILLIN DERIVATIVE (DOTA-AMPICILLIN), WITH HIGH AFFINITY FOR B-LACTAMASE, RADIOACTIVELY LABELED WITH GALLIUM (68GA). ACTION PLAN: 1) GENERATE A STABLE CELL LINE EXPRESSING THE B-LACTAMASE GENE UNDER THE CONTROL OF THE CYTOMEGALOVIRUS (CMV) PROMOTER; 2) INJECTION OF THE POSITIVE B-LACTAMASE CELLS IN MICE TO GENERATE A XENOGRAFT; 3) SYSTEMIC ADMINISTRATION OF 68GALLIUM-AMPICILLIN; AND 4) IMAGE OF THE IN VIVO DISTRIBUTION BY PET.

MAGNETIC RESONANCE IMAGING OF ACTIVE NEURAL PATHWAYS

MAGNETIC RESONANCE IMAGING OF ACTIVE NEURAL PATHWAYS


THE ABILITY TO DETECT AND MEASURE NON-INVASIVELY THE PROPAGATION OF ELECTRICAL ACTIVITY ALONG A NEURAL PATHWAY IN REAL TIME AND WITH A SPATIAL RESOLUTION THAT ALLOWS THE IDENTIFICATION OF THE ANATOMICAL PATH IN THE WORKING HUMAN BRAIN IS AMONG THE MOST RELEVANT, AMBITIOUS AND SO FAR UNSOLVED PROBLEMS IN NEUROSCIENCE. TECHNOLOGIES SUCH AS ELECTRO-ENCEPHALOGRAPHY (EEG) AND MAGNETO-ENCEPHALOGRAPHY (MEG) OR FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) HAVE NOT ACCOMPLISHED THIS TASK YET. THE MAIN AIM OF THIS PROPOSAL IS TO DEMONSTRATE THAT A NEW TECHNIQUE GROUNDED ON BASIC ANATOMICAL, PHYSIOLOGICAL AND PHYSICAL-CHEMICAL PRINCIPLES AND DIFFUSION IMAGING THEORY WILL ALLOW US TO DERIVE DIRECT MEASUREMENTS OF ELECTRICAL ACTIVITY IN ANATOMICAL BRAIN CONNECTIONS IN VIVO. NON-INVASIVE FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI) ALLOWS US TO MAP THE DISTRIBUTED NEURAL SYSTEMS ACTIVATED BY SPECIFIC PARADIGMS. HOWEVER, THE DYNAMIC ELECTRICAL ACTIVITY CARRIED BY THE THOUSANDS OF CONNECTIONS BETWEEN THESE BRAIN AREAS REMAINS TO BE ELUCIDATED. MEASUREMENTS OF WATER MOLECULE DIFFUSION ALONG FIBER TRACTS BY DIFFUSION MAGNETIC RESONANCE IMAGING PROVIDES A STATIC MAP THE NEURAL CONNECTIONS BETWEEN BRAIN CENTERS, BUT DOES NOT CAPTURE THE ELECTRICAL ACTIVITY ALONG THE AXONS OF THESE FIBER TRACTS. HEREIN WE PROPOSE TO TEST A MODEL FOR DIFFUSION MRI BASED ON A HYPOTHESIZED ¿ANISOTROPY REDUCTION DUE TO AXONAL EXCITATION¿ (¿AREX¿) AND EXAMINE THE POTENTIAL CHANGES IN WATER MOBILITY ACCOMPANYING THE MOVEMENT OF IONS DURING THE PROPAGATION OF ACTION POTENTIALS ALONG AXONAL TRACTS. AS THIS MODEL EXAMINES THE PERPENDICULAR MOVEMENT OF WATER MOLECULES (ACCOMPANYING THE MOVEMENT OF IONS) DUE TO THE PROPAGATION OF ACTION POTENTIALS ALONG AXONAL TRACTS, WE PROPOSE THAT THE MEASUREMENT OF WATER MOLECULE DIFFUSION THAT RELIES ON THESE DYNAMIC PROPERTIES OF AXON TRACTS BE TERMED DYNAMIC DIFFUSION IMAGING (DDI).