Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity

OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH. STUDY DESIGN: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15-30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson\u27s partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores. RESULTS: CSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966). CONCLUSION: CSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability

Modelling Point Referenced Spatial Count Data: A Poisson Process Approach

Gaussian random field, Gaussian copula, Pairwise likelihood function, Poisson distribution, Renewal proces

Tendencias de investigación básica y desarrollo tecnológico para la cadena productiva de cacao 2012

Como parte de la estructuración del Sistema Nacional de Ciencia y Tecnología Agropecuaria (SNCTA), como iniciativa clave para el fortalecimiento y consolidación de una visión compartida entorno al direccionamiento estratégico que debe tener la investigación del sector, el desarrollo de apuestas productivas y la estructuración de una línea de base. Es necesario conocer el estado actual a nivel mundial de las tendencias en investigación y desarrollo, para las diferentes cadenas productivas del país.Cacao-Theobroma caca

Immune activation during Paenibacillus brain infection in African infants with frequent cytomegalovirus co-infection

Inflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was

Preterm intraventricular hemorrhage in vitro: Modeling the cytopathology of the ventricular zone

BACKGROUND: Severe intraventricular hemorrhage (IVH) is one of the most devastating neurological complications in preterm infants, with the majority suffering long-term neurological morbidity and up to 50% developing post-hemorrhagic hydrocephalus (PHH). Despite the importance of this disease, its cytopathological mechanisms are not well known. An in vitro model of IVH is required to investigate the effects of blood and its components on the developing ventricular zone (VZ) and its stem cell niche. To address this need, we developed a protocol from our accepted in vitro model to mimic the cytopathological conditions of IVH in the preterm infant. METHODS: Maturing neuroepithelial cells from the VZ were harvested from the entire lateral ventricles of wild type C57BL/6 mice at 1-4 days of age and expanded in proliferation media for 3-5 days. At confluence, cells were re-plated onto 24-well plates in differentiation media to generate ependymal cells (EC). At approximately 3-5 days, which corresponded to the onset of EC differentiation based on the appearance of multiciliated cells, phosphate-buffered saline for controls or syngeneic whole blood for IVH was added to the EC surface. The cells were examined for the expression of EC markers of differentiation and maturation to qualitatively and quantitatively assess the effect of blood exposure on VZ transition from neuroepithelial cells to EC. DISCUSSION: This protocol will allow investigators to test cytopathological mechanisms contributing to the pathology of IVH with high temporal resolution and query the impact of injury to the maturation of the VZ. This technique recapitulates features of normal maturation of the VZ in vitro, offering the capacity to investigate the developmental features of VZ biogenesis

Anxiety-related endophenotypes and hazardous alcohol use in young adults are associated with a functional polymorphism in the SLC6A4 gene

Background: A functional polymorphism (5-HTTLPR, rs4795541) in the serotonin transporter (SLC6A4) gene has been shown as an important candidate for several psychiatric and behavioral traits. Objective: The objective of this study was to examine the possible interaction of this polymorphism with physical neglect in childhood on the presentation of anxiety traits and hazardous alcohol consumption in young Colombian subjects. Methods: 272 young adults (mean age: 21.3 years) were evaluated with the Childhood Trauma Questionnaire, the Zung Self-rating Anxiety Scale, the Big Five Inventory, the Cohen's Perceived Stress Scale, the Alcohol, Smoking, Substance Involvement Screening Test and the Alcohol Use Disorders Identification Test. Genotyping for the 5-HTTLPR polymorphism was carried out using conventional PCR. A linear regression model, corrected by age and gender, was used. Results: We found that individuals with the L/L genotype showed higher scores on physical neglect (p=0.0047), anxiety symptoms (p=0.028), neuroticism (p=0.019) and perceived stress (p=0.035). L/L genotype was a risk factor for hazardous alcohol use in young adults (OR=3.06, p=0.0003). No GxE interactions were observed in our data. Conclusion: Our results provide novel evidence for the role of a functional polymorphism in the SLC6A4 gene on the relationship of childhood trauma, anxiety-related traits and risky consumption of alcohol

Depressive symptoms are associated with a functional polymorphism in a miR-433 binding site in the FGF20 gene

Genetic studies of major depressive disorder and its associated endophenotypes are useful for the identification of candidate genes. In recent years, variations in non-coding RNA genes, such as miRNAs, have been explored as novel candidates for psychiatric disorders and related endophenotypes. The aim of the present study was to evaluate the possible association between a functional polymorphism (rs12720208) in the FGF20 gene, which regulates its modulation by miR-433, and depressive symptoms in young adults. A sample of 270 participants from Colombia were evaluated with the Hospital Anxiety and Depression Scale - Depression Subscale (HADS-D) and genotyped for the rs12720208 polymorphism using a TaqMan assay. A lineal regression analysis was used. A statistically significant association of the functional polymorphism in the FGF20 gene (rs12720208) with depressive symptoms was found. It was observed that individuals with the G/A genotype had higher scores for the HADS-D subscale. Our results are the first description in the scientific literature about a significant association between a functional polymorphism in the FGF20 gene, which regulates its modulation by miR-433, and depressive symptoms

Mechanical Properties of Chaperone BiP, the Master Regulator of the Endoplasmic Reticulum

Immunoglobulin heavy-chain-binding protein (BiP protein) is a 75-kDa Hsp70 monomeric ATPase motor that plays broad and crucial roles maintaining proteostasis inside the cell. Its malfunction has been related with the appearance of many and important health problems such as neurodegenerative diseases, cancer, and heart diseases, among others. In particular, it is involved in many endoplasmic reticulum (ER) processes and functions, such as protein synthesis, folding, and assembly, and also it works in the posttranslational mechanism of protein translocation. However, it is unknown what kind of molecular motor BiP works like, since the mechanochemical mechanism that BiP utilizes to perform its work during posttranslational translocation across the ER is not fully understood. One novel approach to study both structural and catalytic properties of BiP considers that the viscoelastic regime behavior of the enzymes (considering them as a spring) and their mechanical properties are correlated with catalysis and ligand binding. Structurally, BiP is formed by two domains, and to establish a correlation between BiP structure and catalysis and how its conformational and viscoelastic changes are coupled to ligand binding, catalysis, and allosterism (information transmitted between the domains), optical tweezers and nano-rheology techniques have been essential in this regard

Multi-omic analysis elucidates the genetic basis of hydrocephalus.

We conducted PrediXcan analysis of hydrocephalus risk in ten neurological tissues and whole blood. Decreased expression of MAEL in the brain was significantly associated (Bonferroni-adjusted p < 0.05) with hydrocephalus. PrediXcan analysis of brain imaging and genomics data in the independent UK Biobank (N = 8,428) revealed that MAEL expression in the frontal cortex is associated with white matter and total brain volumes. Among the top differentially expressed genes in brain, we observed a significant enrichment for gene-level associations with these structural phenotypes, suggesting an effect on disease risk through regulation of brain structure and integrity. We found additional support for these genes through analysis of the choroid plexus transcriptome of a murine model of hydrocephalus. Finally, differential protein expression analysis in patient cerebrospinal fluid recapitulated disease-associated expression changes in neurological tissues, but not in whole blood. Our findings provide convergent evidence highlighting the importance of tissue-specific pathways and mechanisms in the pathophysiology of hydrocephalus

Gas injection laboratory experiments on Opalinus clay.

Understanding gas transport processes is one of the key issues in the assessment of radioactive waste repository performance and is the focus of this research. To this aim, this research programme was started with the following specific objectives. 1) To develop and calibrate an experimental set-up to perform controlled flow-rate gas injection experiments using a high-pressure triaxial cell to apply isotropic/anisotropic stress states. 2) To carry out a series of tests on Opalinus clay OPA samples to study the conditions under which gas breakthrough processes occur, to analyse the influence of the gas injection rate, the stress state, the orientation of rock discontinuities and other relevant hydro-mechanical variables (porosity, degree of saturation, …), as well as the observation of the induced desaturation (pore water displacement by gas), ingoing and outgoing gas fluxes, aperture and preferential paths created, and so on.Peer ReviewedPostprint (author’s final draft