Background: Brain-derived neurotrophic factor (BDNF) plays an important role in brain development by regulating multiple pathways within the central nervous system. In the Human Biomonitoring for Europe Project (HBM4EU), this neurotrophin is being implemented as a novel effect biomarker to evaluate the potential threats of environmental chemicals on neurodevelopment.
Objectives: To explore the relationships among exposure to environmental metals, BDNF biomarkers at two levels of biological complexity, and behavioral function in adolescent males.
Purpose: Single cell (sc) analyses of key embryonic, fetal and adult stages were performed to generate a comprehensive single cell atlas of all the corneal and adjacent conjunctival cell types from development to adulthood.
Methods: Four human adult and seventeen embryonic and fetal corneas from 10 to 21 post conception week (PCW) specimens were dissociated to single cells and subjected to scRNA- and/or ATAC-Seq using the 10x Genomics platform. These were embedded using Uniform Manifold Approximation and Projection (UMAP) and clustered using Seurat graph-based clustering.
Development of the retina is regulated by growth factors, such as insulin-like growth factors 1 and 2 (IGF-1/2), which coordinate proliferation, differentiation, and maturation of the neuroepithelial precursors cells. In the circulation, IGF-1/2 are transported by the insulin growth factor binding proteins (IGFBPs) family members. IGFBPs can impact positively and negatively on IGF-1, by making it available or sequestering IGF-1 to or from its receptor.
View Article and Find Full Text PDFTools to assess diet in a reliable and efficient way are needed, particularly in children and adolescents. In this study, we assess the reproducibility and validity of a semiquantitative food frequency questionnaire (FFQ) among adolescents in Spain. We analyzed data of 51 male adolescents aged 15-17 years from a prospective birth cohort study.
View Article and Find Full Text PDFObjective: To examine the association of urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), lead (Pb), manganese (Mn), and chromium (Cr) with blood pressure (BP) and serum hormone levels in male adolescents.
Methods: Participants were selected from the INMA (Environment and Childhood)-Granada cohort at their follow-up visit when aged 15-17 years. Metal concentrations were measured in urine samples using inductively coupled plasma mass spectrometry.
Curr Alzheimer Res
December 2016
New concepts about Alzheimer's disease (AD), considered as a clinical-biological entity, make essential the definition of biomarkers that could be used for the in vivo diagnosis of the disorder before dementia develops. Different types of genetic, biochemical and neuroimaging markers have been described, highlighting some of the changes that occur in the brain during the course of the disease, yet there is little proof of their pathognomonic and diagnostic value. Furthermore, many of the assays used are difficult to perform, the equipment/reagents are expensive or potentially hazardous (e.
View Article and Find Full Text PDFUsing Raman and infrared spectroscopy, we monitored spectral changes occurring in the blood plasma of patients with Alzheimer's disease (AD) in relation to healthy controls. The protein secondary structure as reflected by amide I band involves β-sheet enrichment, which may be attributable to Aβ peptide formation and to increasing proportion of the globulins that are β-sheet rich. Likewise, the behavior of the infrared 1200-1000-cm(-1) region and the Raman 980-910- and 450-400-cm(-1) regions can be explained in terms of the said plasma composition change.
View Article and Find Full Text PDFIn this study we have determined whether Raman and infrared spectroscopy of blood plasma differentiates Alzheimer's disease (AD) from normal aging of healthy controls. Spectroscopic analysis was conducted on blood plasma samples from 8 mild AD, 16 moderate AD, 11 severe AD, and 12 normal elderly control persons using Fourier transform spectrometers and a near-infrared laser beam as excitation source for Raman spectroscopy. Spectra were processed employing discriminant analysis to determine whether band areas and frequency-intensity relationships might reveal biochemical differences associated with AD.
View Article and Find Full Text PDFPeripheral mononuclear leukocytes from Alzheimer's disease (AD) patients were analyzed by infrared spectroscopy and their spectroscopic properties were compared with those from age-matched healthy controls. Two-dimensional correlation analysis of mean spectra measured at various disease stages shows that the protein secondary structure from AD patients involves β-sheet enrichment and carbonyl intensity increase relative to healthy controls. The area percentages of β-sheets, which were obtained by using a peak ratio second-derivative spectral treatment, were used for receiver operating characteristic (ROC) analysis to distinguish between patients with AD and age-matched healthy controls.
View Article and Find Full Text PDFThe secondary structure of the loop IIId domain in the RNA of hepatitis C virus (HCV) is well-conserved among different genotypes of HCV, which suggests that the nucleocapsid proteins may interact with the genome RNA through this loop structure. Using infrared spectroscopy, we monitored structural changes occurring in HCV core protein and loop IIId upon formation of nucleocapsid-like particles (NLPs). The protein secondary structure of these particles involves beta-sheet enrichment in relation to its protein monomer.
View Article and Find Full Text PDFAnal Bioanal Chem
February 2009
We describe the improvement of a novel approach to investigating hydrogen/deuterium (H/D) exchange kinetics in biomolecules using transmission infrared spectroscopy. The method makes use of a Fourier transform infrared spectrometer coupled with a microdialysis flow cell to determine exchange rates of labile hydrogens. With this cell system, the monitoring of exchange reactions has been studied here as a function of some cell characteristics such as: (a) dialysis membrane surface contacting both the H(2)O and D(2)O compartments; (b) molecular cutoff of dialysis membrane; and (c) distance between the cell-filling holes.
View Article and Find Full Text PDFMolecular interactions required for hepatitis C virus (HCV) assembly are not well known and are poorly understood. The 5' untranslated region (5'UTR) of the RNA genome is highly conserved and has extensive secondary structure, and the highly basic core protein is rich in arginine residues. Using Raman and circular dichroism (CD) spectroscopies, specific interactions have been demonstrated here between the 5'UTR sequence and the core protein that may be important for the specific encapsidation of the viral genome during HCV replication.
View Article and Find Full Text PDFElectron microscopy and infrared and Raman spectroscopy have been used here to study the morphology, size distribution, secondary and tertiary structures of protein particles assembled from a truncated hepatitis C virus (HCV) core protein covering the first 120 aa. Particles of pure protein, having similar morphology and size distribution of those of nucleocapsids found in sera from HCV-infected patients, have been visualized for the first time. The secondary structure of these protein particles involve beta-sheet enrichment in relation to its protein monomer.
View Article and Find Full Text PDFRaman and FTIR spectroscopy have been used to characterize the structure of 5'untranslated region (5'UTR, 342-mer RNA) of the HCV genome. The study of the 750-850 cm(-1) Raman spectral domain of the ribose-phosphate backbone reveals that the percentage of nucleobases involved in double helix-loop junctions is 19+/-1%, which is very close to that of a theoretical secondary structure model (18.7%) proposed on the basis of comparative sequence analysis and thermodynamic modelling.
View Article and Find Full Text PDFWe present here a new accessory for IR transmission measurements of 1H/2H exchange, as an ancillary tool for monitoring structural features of biomolecules in aqueous solution. This new accessory results from the combination of two dialysis membranes and a conventional liquid cell having two cylinders containing 2H2O buffer. When compared with conventional transmission measurements, carried out either after dissolving lyophilized biomolecules in 2H2O or after dialyzing the aqueous solution considered against 2H2O buffer, this accessory shows the following advantages: (1) controlled measurements over the initial steps of this isotopic exchange and absence of molecular aggregation, and (2) smaller sample amounts.
View Article and Find Full Text PDFHCVc 120 is a truncated protein from the hepatitis C virus (HCV) core protein that interacts with itself to form nucleocapsid-like particles. We present here the infrared and Raman spectra of oligomeric HCVc 120 protein in order to obtain insights into its secondary structure as well as the environment surrounding some protein side chains. When compared with its monomer form, oligomeric HCVc 120 protein shows an increase in beta-sheet structure.
View Article and Find Full Text PDFThe complex between adenosine triphosphate (ATP) and 4-guanidinobutyric acid (GBA) has been studied by infrared spectroscopy dry and hydrated (60% relative humidity). Partial nonenzymic hydrolysis has been detected, as deduced from characteristic bands of adenosine diphosphate (ADP) and inorganic orthophosphate formation. An infrared continuum, which increases upon hydration, demonstrates that the hydrogen bonded system in this complex has a large proton polarizability due to collective proton fluctuation.
View Article and Find Full Text PDFWe have studied the thermal denaturation of native basic pancreatic trypsin inhibitor (BPTI) by monitoring the Raman bands in the 4000-400 cm(-1) range. In agreement with results obtained by calorimetry, a cooperative melting transition is observed starting at 75 degrees C. This transition is found to involve predominantly the unfolding of helical structures accompanied by beta-aggregation, loss of hydrophobic interactions between side chains and changes in CSSC dihedral angles.
View Article and Find Full Text PDFInfrared and UV spectroscopies have been used to study the assembly of a hairpin nucleotide sequence (nucleotides 3-30) of the 5' non-coding region of the hepatitis C virus RNA (5'-GGCGGGGAUUAUCCCCGCUGUGAGGCGG-3') with a RNA 20mer ligand (5'-CCGCCUCACAAAGGUGGGGU-3') in the presence of magnesium ion and spermidine. The resulting complex involves two helical structural domains: the first one is an intermolecular duplex stem at the bottom of the target hairpin and the second one is a parallel triplex generated by the intramolecular hairpin duplex and the ligand. Infrared spectroscopy shows that N-type sugars are exclusively present in the complex.
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