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"Roncal, Maria"
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Intranasal epidermal growth factor treatment rescues neonatal brain injury
2014
Diffuse white matter injury is common in very preterm infants; here, enhanced epidermal growth factor receptor signalling in oligodendrocyte precursor cells in a mouse model of such injury is shown to increase cellular and functional recovery.
EGFR treatment of neonatal brain injury
As the survival rates of premature babies have increased, so too has the incidence of chronic neurodevelopmental disorders in neonates. Diffuse white matter injury is common in preterm infants with neonatal brain injury and is partially the result of a failure in oligodendrocyte precursor cell maturation. Here, Vittorio Gallo and colleagues specifically enhanced epidermal growth factor receptor (EGFR) signalling in oligodendrocyte precursor cells in a model of diffuse white matter injury and found increased cellular and functional recovery post-injury. Oligodendrocyte cell death was decreased and the generation of new oligos was increased by the treatment. This identifies EGFR signalling as a potential therapeutic target in the treatment of premature children after white matter injury.
There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks’ gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments
1
,
2
. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI
3
. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development
4
. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.
Journal Article
Intranasal epidermal growth factor treatment rescues neonatal brain injury
by
Hammond, Timothy R.
,
Jablonska, Beata
,
Scafidi, Joseph
in
Brain
,
Children
,
Epidermal growth factor
2014
Diffuse white matter injury is common in very preterm infants; here, enhanced epidermal growth factor receptor signalling in oligodendrocyte precursor cells in a mouse model of such injury is shown to increase cellular and functional recovery.
Journal Article
Laboratory and clinical practices in antinuclear antibody detection and related antigens: recommendations from a Spanish multicentre survey
by
Hoyos, Marcos López
,
Mariscal, Anaís
,
Sacristán, Beatriz
in
Anti-DNA antibodies
,
Antigens
,
Antinuclear antibodies
2023
Antinuclear antibodies (ANA) are the most widely used immunological test for the diagnosis of autoimmune diseases. Despite the recommendations of experts, there is some variability in performing and interpreting this test in routine practice. In this context, the Spanish Group on Autoimmune Diseases (GEAI) of the Spanish Society of Immunology (SEI) conducted a national survey of 50 autoimmunity laboratories. Here we report the survey results on ANA testing, detection of related antigens, and our recommendations. The survey showed that most of the participating laboratories use a similar approach for most key practices: 84% perform ANA by indirect immunofluorescence (IIF) on HEp-2 cells as the screening methodology while the other laboratories use IIF to confirm positive screens; 90% report ANA test results as either negative or positive with titer and pattern; 86% indicated that the ANA pattern conditioned follow-up testing for specific antigen-related antibodies; and 70% confirm positive anti-dsDNA. However, testing practices were highly heterogeneous for certain items, such as sera dilutions and the minimum time period for repeating ANA and related antigen determinations. Overall, this survey shows that most autoimmune laboratories in Spain use a similar approach but that further standardization of testing and reporting protocols is needed.
Journal Article
Planeamiento Estratégico para la Región Lima Provincias
by
Mendoza Roncal, Anabary Maria
,
Gutierrez Vizcarra, Jorge Luis
,
Morales Rojas, Kelly Anne
in
Economics
,
Latin American Studies
2018
El presente trabajo desarrolla el plan estratégico de la Región Lima Provincias, una región que posee un alto potencial para desarrollar, debido a que cuenta con una gran variedad de recursos que pueden aprovecharse de mejor manera mediante los Tratados de Libre Comercio y así aportar al dinamismo de la economía nacional. La metodología utilizada para la formulación de este plan se ha basado en el Modelo Secuencial del Proceso Estratégico desarrollado por el profesor Fernando D’Alessio. Para ello se revisó información bibliográfica basada en fuentes confiables y a partir de ella se pudo conocer la situación actual de la región; asimismo, se realizó un análisis externo e interno para establecer objetivos de corto y largo plazo, los cuales se llevarán a cabo mediante la formulación, implementación y evaluación de estrategias, con el fin de alcanzar la visión deseada, de que para el 2025 Lima Provincias sea una región estratégica, líder en agroexportación y turismo, moderna, autosostenible y generadora de oportunidades, asegurando que el uso de los recursos impacten positivamente en el medio ambiente y que repercuta en una mejor calidad de vida de los ciudadanos. El logro de la visión dependerá del cumplimiento de los objetivos de corto y largo plazo, además, el Tablero de Control Balanceado (Balance Scorecard) permitirá monitorear el cumplimiento y medir los resultados de los objetivos a corto plazo. Mediante la aplicación del presente plan estratégico, la Región Lima Provincias se consolidará como un actor fundamental de la economía nacional y mundial
Dissertation
Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease
by
Moreno-Jiménez, Elena P
,
Flor-García, Miguel
,
Pallas-Bazarra Noemí
in
Aging
,
Alzheimer's disease
,
Brain
2019
The hippocampus is one of the most affected areas in Alzheimer’s disease (AD)1. Moreover, this structure hosts one of the most unique phenomena of the adult mammalian brain, namely, the addition of new neurons throughout life2. This process, called adult hippocampal neurogenesis (AHN), confers an unparalleled degree of plasticity to the entire hippocampal circuitry3,4. Nonetheless, direct evidence of AHN in humans has remained elusive. Thus, determining whether new neurons are continuously incorporated into the human dentate gyrus (DG) during physiological and pathological aging is a crucial question with outstanding therapeutic potential. By combining human brain samples obtained under tightly controlled conditions and state-of-the-art tissue processing methods, we identified thousands of immature neurons in the DG of neurologically healthy human subjects up to the ninth decade of life. These neurons exhibited variable degrees of maturation along differentiation stages of AHN. In sharp contrast, the number and maturation of these neurons progressively declined as AD advanced. These results demonstrate the persistence of AHN during both physiological and pathological aging in humans and provide evidence for impaired neurogenesis as a potentially relevant mechanism underlying memory deficits in AD that might be amenable to novel therapeutic strategies.Newborn neurons are continuously incorporated into the healthy adult human hippocampus up to the ninth decade of life. However, robust adult hippocampal neurogenesis sharply declines during the progression of Alzheimer’s disease.
Journal Article
Cardiovascular risk factors among adult patients with haemophilia
by
Caram-Deelder Camila
,
Camelo Ricardo Mesquita
,
de Moura Marilia Carolina Braga
in
Age related diseases
,
Aging
,
Blood levels
2021
Since the introduction of episodic and prophylactic treatments with safer factor concentrates, the life expectancy of people with haemophilia (PwH) has improved considerably. Ageing-related diseases such as cardiovascular disease (CVD) have also become more prevalent in PwH. This cross-sectional study aimed to evaluate CVD risk factors and estimate 10-year risk for CVD events among PwH. Male patients ≥ 30 years were interviewed and examined. Blood tests were performed at the local laboratory. Eighty-two patients were included, of whom 83% had haemophilia A and half had severe disease. Median age at study entry was 43.0 years (interquartile range [IQR], 36.0–51.3). Prevalence of obesity, systemic arterial hypertension (SAH) and diabetes mellitus were 16%, 60% and 16%, respectively. Hypertriglyceridaemia, hypercholesterolaemia and low HDL blood levels were present in 18%, 41% and 30% of patients, respectively. Metabolic syndrome was found in 37%. The Framingham Risk Score showed that 39% of PwH had a high risk of developing cardiovascular events in the following 10 years. We conclude that, in this cohort, PwH have a higher prevalence of SAH when compared with Brazilian men without haemophilia and about two-fifths have a high risk of developing a CVD event in the following 10 years.
Journal Article
Targeted Capture of Hundreds of Nuclear Genes Unravels Phylogenetic Relationships of the Diverse Neotropical Palm Tribe Geonomateae
2019
The tribe Geonomateae is a widely distributed group of 103 species of Neotropical palms which contains six ecologically important understory or subcanopy genera. Although it has been the focus of many studies, our understanding of the evolutionary history of this group, and in particular of the taxonomically complex genus
, is far from complete due to a lack of molecular data. Specifically, the previous Sanger sequencing-based studies used a few informative characters and partial sampling. To overcome these limitations, we used a recently developed Arecaceae-specific target capture bait set to undertake a phylogenomic analysis of the tribe Geonomateae. We sequenced 3,988 genomic regions for 85% of the species of the tribe, including 84% of the species of the largest genus,
. Phylogenetic relationships were inferred using both concatenation and coalescent methods. Overall, our phylogenetic tree is highly supported and congruent with taxonomic delimitations although several morphological taxa were revealed to be non-monophyletic. It is the first time that such a large genomic dataset is provided for an entire tribe within the Arecaceae. Our study lays the groundwork not only for detailed macro- and micro-evolutionary studies within the group, but also sets a workflow for understanding other species complexes across the tree of life.
Journal Article
GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
by
Llorens-Martín, María
,
Hernández-Vivanco, A.
,
Rodríguez-Moreno, C. B.
in
Adult
,
adults
,
axons
2023
Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3β) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3β-overexpressing newborn neurons show an increased number and altered size of Gephyrin
+
postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3β overexpression triggers a depletion of Parvalbumin
+
interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3β is dysregulated.
Journal Article
Pleurotus ostreatus Mycelium and Sugarcane Bagasse as Substitute Environment-Friendly Material for Polystyrene Foam
by
Rojas-Villacorta, Walter
,
Quezada-Alvarez, Medardo A.
,
Siche, Raúl
in
Agribusiness
,
Biomedical materials
,
Carbon dioxide
2023
Biodiversity in ecosystems is threatened by plastic waste, a significant pollution problem. The research aims to use plastic, Pleorotus ostreatus mycelium, and sugarcane bagasse to develop an eco-friendly biomaterial. The preparation consisted of three phases: (1) Treatment of the underlying layer, (2) inoculation of the fungus (three different concentrations: 15%, M1; 20%, M2; and 25%, M3), and (3) dehydration of the biomaterial. The physical characterization results (density, water absorption, and texture) showed that the average density varies between 127.86 and 131.19 kg/m3; also, the M1 sample had a high percentage of water absorption (23.55%), while M2 obtained lower percentages (11.79%). In the bending test, samples M2 and M3 showed higher structural resistance with stress values of 0.682 and 0.68 MPa, respectively. Based on the results, the produced biomaterials may serve as an alternative to expanded polystyrene (EPS). Due to their moldable characteristics, they can be used in non-structural construction, packaging, and various architectural applications. The research provided promising results; however, additional parameters must be evaluated to be able to commercialize them.
Journal Article