Publications

Factor VIII gene transfer with a single intravenous infusion of valoctocogene roxaparvovec (AAV5-hFVIII-SQ) has demonstrated clinical benefits lasting 5 years to date in people with severe hemophilia A. Molecular mechanisms underlying sustained AAV5-hFVIII-SQ-derived FVIII expression have not been studied in humans. In a substudy of the phase 1/2 clinical trial ( NCT02576795 ), liver biopsy samples were collected 2.6-4.1 years after gene transfer from five participants.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection.

Homologous recombination (HR)-based gene therapy using adeno-associated viruses (AAV-HR) without nucleases has several advantages over classic gene therapy, especially the potential for permanent transgene expression. However, the low efficiency of AAV-HR remains a major limitation. Here, we tested a series of small-molecule compounds and found that ribonucleotide reductase (RNR) inhibitors substantially enhance AAV-HR efficiency in mouse and human liver cell lines approximately threefold.

A dor é uma experiência sensorial e emocional, comumente iniciada em resposta a um estímulo nóxico. Um grupo de neurónios sensoriais periféricos, conhecidos como nociceptores, são os primeiros neurónios a serem ativados pelo estímulo nóxico. Os corpos celulares dos neurónios sensoriais estão alojados no gânglio do trigémeo (TG) ou no gânglio raquidiano dorsal (DRG), situados bilateralmente e adjacentes ao tronco cerebral ou coluna vertebral.

Abstract Unavailable

The adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in pre-pubertal, 3-week-old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle three weeks later.

This volume contains experimental approaches that are currently revolutionizing our understanding of the neurobiology of pain.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal-dominant disorder caused by an expanded pentanucleotide repeat in the ATXN10 gene. This repeat expansion, when fully penetrant, has a size of 850 to 4500 repeats. It has been shown that the repeat composition can be a modifier of disease, e.g., seizures.Here, we describe a Hispanic kindred in which we identified both pure (ATTCT)n expansions and mixed (ATTCT)n-(ATTCC)n in the same family. We used No-Amp targeted sequencing and optical genome mapping to decipher the composition of these repeat expansions.

: P2X3 purinoceptors are expressed by airway sensory neurons and are activated by extracellular ATP released during periods of cell stress. In asthma, sensitivity to ATP is increased. Airway eosinophilia, which is common in a majority of asthmatics, increases airway epithelial sensory nerve density in mice and in humans. Whether eosinophils increase neuronal P2X3 expression in asthma is unknown.

RATIONALE: Idiopathic Pulmonary Fibrosis (IPF) is an age-related progressive and fatal lung disease with limited therapeutic options. IPF exhibits several pathological features of epithelial reprogramming, including cellular senescence. Moreover, distal airway remodeling and bronchiolization can result in honeycomb cysts. The molecular and cellular mechanisms that lead to this prominent phenotype, however, still remain poorly characterized. Here, we aimed to decipher the IPF distal bronchiole and alveolar cell subtypes and their potential contribution to IPF development and progression.