A5022777211- Respiratory viral infections research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Thyroid Disorders and Treatments
- Viral gastroenteritis research and epidemiology
- Protein Kinase Regulation and GTPase Signaling
- Bacteriophages and microbial interactions
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Genetic Syndromes and Imprinting
- Congenital heart defects research
- RNA modifications and cancer
- Ion channel regulation and function
- Peptidase Inhibition and Analysis
- Alzheimer's disease research and treatments
- Viral Infections and Immunology Research
- Neonatal Respiratory Health Research
- Long-Term Effects of COVID-19
- Viral Infections and Outbreaks Research
- Virology and Viral Diseases
- RNA Research and Splicing
- Animal Virus Infections Studies
- Cellular transport and secretion
- COVID-19 Clinical Research Studies
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Pneumonia and Respiratory Infections
Consejo Nacional de Investigaciones Científicas y Técnicas
2012-2025
National University of General San Martín
2025
Universitat Autònoma de Barcelona
2016-2025
Infant Foundation
2020-2023
Fundación Instituto Leloir
2011-2023
National Research Council
2021
Centro Científico Tecnológico - Tucumán
2020
University of Buenos Aires
2001-2010
Hospital de Clínicas "José de San Martín"
2003
University of California, San Francisco
2003
Therapies to interrupt the progression of early coronavirus disease 2019 (Covid-19) remain elusive. Among them, convalescent plasma administered hospitalized patients has been unsuccessful, perhaps because antibodies should be earlier in course illness.We conducted a randomized, double-blind, placebo-controlled trial with high IgG titers against severe acute respiratory syndrome 2 (SARS-CoV-2) older adult within 72 hours after onset mild Covid-19 symptoms. The primary end point was disease,...
Abstract Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological aggregation. Native state stabilizers are promising drugs to treat Here we repurpose tolcapone, an FDA-approved molecule for Parkinson’s disease, as potent aggregation inhibitor. Tolcapone binds specifically human plasma, stabilizes the native vivo mice and humans inhibits cytotoxicity. Crystal structures of tolcapone bound wild-type V122I...
Hereditary transthyretin amyloidosis (ATTR) is a disease characterized by the extracellular deposition of (TTR) amyloid fibrils. Highly destabilizing TTR mutations cause leptomeningeal amyloidosis, rare, but fatal, disorder in which aggregates brain. The remains intractable, since liver transplantation, reference therapy for systemic ATTR, does not stop mutant production In addition, despite current pharmacological strategies have shown to be effective against vivo aggregation stabilizing...
The MIA40 relay system mediates the import of small cysteine-rich proteins into intermembrane mitochondrial space (IMS). substrates are synthesized in cytosol and assumed to be disordered their reduced state this compartment. As they cross outer membrane, promotes oxidation critical native disulfides facilitate folding, trapping functional species IMS. Here, we study redox-controlled folding TRIAP1, a protein with moonlighting function: regulating phospholipid trafficking between membranes...
The tumor suppressor p53 modulates the transcription of a variety genes constituting protective barrier against anomalous cellular proliferation. High frequency hot-spot mutations result in loss- of-function by formation amyloid-like aggregates that correlate with cancerous progression. We show full-length undergoes spontaneous homotypic condensation at sub-micromolar concentrations and absence crowders, to yield dynamic coacervates are stoichiometrically dissolved DNA. These fuse evolve...
Iodide organification defects are associated with mutations in the dual oxidase 2 (DUOX2) gene and characterized by a positive perchlorate discharge test. These produce congenital goitrous hypothyroidism, usually transmitted an autosomal recessive mode.We studied complete coding sequence of human DUOX2 single-strand conformational polymorphism (SSCP) analysis DNA from 17 unrelated patients iodide defects. Samples showing aberrant pattern were directly sequenced. All validated SSCP analysis....
Summary Context Thyroid dyshormonogenesis is associated with mutations in the thyroglobulin (TG) gene and characterized by normal organification of iodide low serum TG. These give rise to congenital goitrous hypothyroidism, transmitted an autosomal recessive mode. Objectives The aim this study was identify new TG attempt increase understanding molecular basis disorder. Three unrelated patients marked impairment synthesis were studied. Methods promoter complete coding regions gene, along...
Abstract Background Many deaths in infants from low-middle income countries (LMICs) occur at home or upon arrival to health facilities. Although acute lower respiratory tract illness plays an important role community mortality, the accuracy of mortality rates due syncytial virus (RSV) remains unknown. Methods An active surveillance study among children aged under 5 years old (U5) was performed Buenos Aires, Argentina, between January and December 2019, define burden RSV childhood mortality....
Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine. We analyzed the TPO gene 14 unrelated patients clinical evidence of organification defects. Seven affected individuals harbored mutations gene; one was compound heterozygous, others were simply heterozygous for mutations. Five novel have been identified, which found be a single nucleotide deletion, while other four...
Paramyxoviruses share the essential RNA polymerase complex components, namely, (L), phosphoprotein (P), and nucleoprotein (N). Human respiratory syncytial virus (RSV) P is smallest polypeptide among family, sharing a coiled coil tetramerization domain, which disruption renders inactive. We show that unfolding of displays first transition with low cooperativity but substantial loss α-helix content accessibility to hydrophobic sites, indicative loose chain packing fluctuating tertiary...
More than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote extracellular deposition of TTR as pathological amyloid fibrils. So far, only R104H T119M have been shown to stabilize significantly TTR, acting disease suppressors. We describe novel A108V non-pathogenic mutation found in Portuguese subject. This variant is more stable wild type both vitro human plasma, feature that...
Abstract Background Therapies to interrupt progression of early COVID-19 remain elusive. Among them, convalescent plasma in hospitalized patients was unsuccessful, perhaps because antibody should be administered earlier. We advanced infusions the first 72 hours symptoms arrest progression. Methods A randomized, double-blind, placebo-controlled trial with high IgG titers against SARS-CoV2 elderly subjects within mild symptoms. The primary endpoint severe respiratory disease defined as a rate...
Intrinsic disorder is at the center of biochemical regulation and particularly overrepresented among often multifunctional viral proteins. Replication transcription respiratory syncytial virus (RSV) relies on a RNA polymerase complex with phosphoprotein cofactor P as structural scaffold, which consists four-helix bundle tetramerization domain flanked by two domains predicted to be intrinsically disordered. Because intrinsic cannot reduced defined atomic structure, we tackled experimental...
Amyloids have been exploited to build amazing bioactive materials. In most cases, short synthetic peptides constitute the functional components of such The controlled assembly globular proteins into active amyloid nanofibrils is still challenging, because formation amyloids implies a conformational conversion towards β-sheet-rich structure, with concomitant loss native fold and inactivation protein. There is, however, remarkable exception this rule: yeast prions. They are singular able...
Thyroid dysgenesis may be associated with mutations in the paired box transcription factor 8 (PAX8) gene and is characterized by congenital hypothyroidism transmitted an autosomal dominant mode.The aim of this study was to identify new PAX8 gene. Sixty hypothyroidism-affected individuals dysgenetic (agenesis, ectopia hypoplasia) eutopic thyroid glands were studied.The 12 exons along their exon-intron boundaries amplified from genomic DNA a mutational screening performed single-strand...
Human respiratory syncytial virus (hRSV) is a worldwide distributed pathogen that causes disease mostly in infants and the elderly. The M2-1 protein of hRSV functions as transcription antiterminator partakes particle budding. It present only Pneumovirinae, namely, Pneumovirus (RSV) Metapneumovirus, making it an interesting target for specific antivirals. tight tetramer bearing Cys3-His1 zinc-binding motif, Ebola VP30 some eukaryotic proteins, whose integrity was shown to be essential...
The human respiratory syncytial virus M(2-1) transcription antiterminator is an essential elongation factor required by the RNA polymerase for effective beyond first two nonstructural genes. Its exclusive presence in pneumovirus among all paramyxovirus suggests a unique function within this small genus. With aim of understanding its biochemical properties, we investigated α-helical tetramer making use biophysical approach. We found that hydrodynamic radius considerably extended at high ionic...
Hereditary transthyretin amyloidosis (ATTR) is an autosomal dominant disease characterized by the extracellular deposition of transport protein (TTR) as amyloid fibrils. Despite progress achieved in recent years, understanding why different TTR residue substitutions lead to clinical manifestations remains elusive. Here, we studied molecular basis disease-causing missense mutations affecting residues R34 and K35. R34G K35T variants cause vitreous amyloidosis, whereas R34T K35N result...