A5085247059- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Neuroscience and Neural Engineering
- Lipid Membrane Structure and Behavior
- Neural dynamics and brain function
- Parasites and Host Interactions
- Electrochemical Analysis and Applications
- Conducting polymers and applications
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Genetic Neurodegenerative Diseases
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
- Endoplasmic Reticulum Stress and Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Parasitic Diseases Research and Treatment
- Mosquito-borne diseases and control
- Seaweed-derived Bioactive Compounds
- Antimicrobial Peptides and Activities
- Toxin Mechanisms and Immunotoxins
- stochastic dynamics and bifurcation
- Neurological disorders and treatments
- Drug Transport and Resistance Mechanisms
University of Cambridge
2019-2025
Instituto de Parasitología y Biomedicina "López - Neyra"
2011-2019
Consejo Superior de Investigaciones Científicas
2011-2019
Super-resolution optical imaging reveals the accumulation of SARS-CoV-2 nucleocapsid protein at viral replication organelles.
Parkinson's disease (PD) is linked to the aggregation of intrinsically disordered protein α-synuclein (aSyn), but precise triggers and mechanisms driving this process remain unclear. Local environmental factors, such as ion concentrations, can influence aSyn's conformational ensemble its tendency aggregate. In study, we explore how physiologically relevant ions, mainly Ca2+ Na+, affect aSyn aggregation, monomer structural dynamics, fibril polymorphism. ThT fluorescence assays show that all...
Advanced optical imaging techniques address important biological questions in neuroscience, where structures such as synapses are below the resolution limit of a conventional microscope. At same time, microelectrode arrays (MEAs) indispensable understanding language neurons. Here, authors show transparent MEAs capable recording action potentials from neurons and compatible with advanced microscopy. The electrodes made conducting polymer poly(3,4-ethylenedioxythiophene) doped polystyrene...
Abstract Background Conventional serological tests, using total soluble proteins or a cocktail of recombinant from T. cruzi as antigens, are highly sensitive for Chagas disease diagnosis. This type however, does not seem to be reliable tools short- and medium-term monitoring the evolution patients after antiparasitic treatment. The aim present study was search immunological markers that could altered in sera benznidazole treatment, therefore have potential predictive diagnostic value....
Mitochondrial dysfunction has long been implicated in the neurodegenerative disorder Parkinson's disease (PD); however, it is unclear how mitochondrial impairment and α-synuclein pathology are coupled. Using specific inhibitors, EM analysis, biochemical assays, we report here that intramitochondrial protein homeostasis plays a major role aggregation. We found interference with proteases, such as HtrA2 Lon protease, import significantly aggravates seeding. In contrast, direct inhibition of...
Monomeric alpha-synuclein (aSyn) is a well characterised protein that importantly binds to lipids. aSyn monomers assemble into amyloid fibrils which are localised lipids and organelles in insoluble structures found Parkinson's disease patient's brains. Previous work address pathological aSyn-lipid interactions has focused on using synthetic lipid membranes, lack the complexity of physiological membranes. Here, we use membranes form synaptic vesicles (SV) isolated from rodent brain...
Drug studies targeting neuronal ion channels are crucial to understand function and develop therapies for neurological diseases. The traditional method study ion-channel activities heavily relies on the whole-cell patch clamp as industry standard. However, this technique is both technically challenging labour-intensive, while involving complexity of keeping cells alive with low throughput. Therefore, shortcomings limiting efficiency ion-channel-related neuroscience research drug testing....
Fluorescence lifetime imaging microscopy (FLIM) is a powerful optical tool widely used in biomedical research to study changes sample's microenvironment. However, data collection and interpretation are often challenging, traditional methods such as exponential fitting phasor plot analysis require high number of photons per pixel for reliably measuring the fluorescence fluorophore. To satisfy this requirement, prolonged acquisition times needed, which makes FLIM low-throughput technique with...
Microelectrode arrays (MEAs) permit recordings with high electrode counts, thus generating complex datasets that would benefit from precise neuronal spike sorting for meaningful data extraction. Nevertheless, conventional methods face limitations in recognizing diverse shapes. Here, we introduce PseudoSorter, which uses self-supervised learning techniques, a density-based pseudolabeling strategy, and an iterative fine-tuning process to enhance accuracy. Through benchmarking, demonstrate the...
ABSTRACT Nowadays, the techniques available for chronic Chagas' disease diagnosis are very sensitive; however, they do not allow discrimination of patient's clinical stages disease. The present paper describes that three out five different repeats contained in Trypanosoma cruzi TcCA-2 membrane protein (3972-FGQAAAGDKPPP, 6303-FGQAAAGDKPAP, and 3973-FGQAAAGDKPSL) recognized with high sensitivity (>90%) by sera from patients acute phase A total 133 serum samples chagasic 50 healthy donors...
During aging, proteostasis capacity declines and distinct proteins become unstable can accumulate as protein aggregates inside outside of cells. Both in disease during selectively aggregate certain tissues not others. Yet, tissue-specific regulation cytoplasmic aggregation remains poorly understood. Surprisingly, we found that the inhibition 3 core quality control systems, namely chaperones, proteasome, macroautophagy, leads to lower levels age-dependent Caenorhabditis elegans pharyngeal...
The initial state of the intrinsically disordered protein α-synuclein (aSyn), e.g., presence oligomers and degradation products, or contaminants adducts can greatly influence aggregation kinetics toxicity protein. Here, we compare four commonly used protocols for isolation recombinant aSyn from Escherichia coli: boiling, acid precipitation, ammonium sulfate periplasmic lysis followed by ion exchange chromatography gel filtration. We identified, using nondenaturing electrospray ionization...
Abstract Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing understanding basis neuronal functions. However, rapid millisecond‐scale fluctuations in subtle sub‐diffraction resolution synaptic morphology pose significant challenges to this endeavor. Here, specially designed graphene microelectrode arrays (G‐MEAs) are used, which compatible with high spatial imaging across various scales as well permit temporal electrophysiological...
One of the current greatest challenges Chagas disease is establishment biomarkers to assess efficacy drugs in a short period time. In this context, reactivity sera from 66 adults with chronic indeterminate (IND) for set four Trypanosoma cruzi antigens (KMP11, PFR2, HSP70, and 3973d) was analyzed before after benznidazole treatment. The results showed that against these decreased at 9, 24, 48 months Moreover, 42.4% 68.75% IND patients met established standard criteria therapeutic (STEC) 24...
The objective was to characterize a Trypanosoma cruzi repetitive amino acid sequence that can be used as marker of therapeutic drug efficacy in patients with chronic Chagas' disease. Reactivities the 3973 peptide were measured 85 disease (41 asymptomatic stage and 44 cardiomyopathy stage) before 9 24 months after benznidazole administration. Additionally, levels IL-6 C-reactive protein serum samples from cardiomyopathy. In 85% 73% symptomatic patients, modifications reactivity observed at...
Abstract Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing our understanding basis neuronal functions. However, rapid millisecond-scale fluctuations in subtle sub-diffraction resolution synaptic morphology pose significant challenges to this endeavour. Here, we use graphene microelectrode arrays (G-MEAs) address these challenges, as they are compatible with high spatial imaging across various scales well temporal...
The enzyme indoleamine 2,3-dioxigenase (IDO) is critical for the regulation of immune responses in pro-tolerogenic antigen-presenting cell. To address profile associated with Chagas disease, we measured IDO activity peripheral blood mononuclear cells from 168 chronic patients and 13 healthy donors. We found that was increased disease when compared controls. Moreover, symptomatic phase, involving cardiac or digestive alterations, higher than detected asymptomatic correlated severity symptoms....
The Alzheimer's disease related peptide, Amyloid-beta (Aβ)1–40 and 1–42, has proven difficult to be purified as a recombinant monomeric protein due its expression in E. coli leading the formation of insoluble inclusion bodies tendency quickly form aggregates. A vast array methods have been used so far, yet many pitfalls, such use tags for ease Aβ isolation, multimers within time frame extraction, or need reconstitute from freeze–dried state. Here, we present rapid protocol produce highly...
Using nanopipette electrophysiology, we reveal in neuronal dendrites a diversity of voltage dynamics comprising firing activity, bursting events and spontaneous transients, including novel class consisting transient sustained hyperpolarisations.
ABSTRACT Parkinson’s Disease (PD) is characterized by the aggregation of alpha-synuclein (aSyn), a presynaptic protein that transitions from disordered monomer into beta-sheet rich amyloid fibrils. The precise triggers and mechanisms underlying aSyn misfolding remain unclear, hindering development effective therapeutics. Monomeric an intrinsically (IDP) with high conformational flexibility. Local environmental factors, such as ion concentrations, can influence ensemble aSyn, impacting its...
Abstract Extracellular recordings of neuronal activity constitute a powerful tool for investigating the intricate dynamics neural networks and individual neurons. Microelectrode arrays (MEAs) allow with high electrode count, ranging from 10s to 1000s, generating extensive datasets information. Furthermore, MEAs capture extracellular field potentials cultured cells, resulting in highly complex signals that necessitate precise spike sorting meaningful data extraction. Nevertheless,...
Abstract Mitochondria have long been implicated in Parkinson’s disease (PD), however, it is not clear how mitochondrial impairment and alpha-synuclein pathology are coupled. We report here that intra-mitochondrial protein homeostasis plays a major role fibril elongation, as interference with proteases import significantly aggravate aggregation. In contrast, direct inhibition of complex I, increase intracellular calcium concentration or formation reactive oxygen species (ROS), all which...