945 research outputs found

    Intercalation processes and diffusion paths of lithium ions in spinel-type structured Li1+xTi2O4: density functional theory study

    Get PDF
    Intercalation processes and corresponding diffusion paths of Li ions into spinel-type structured Li1+xTi2O4 0 x 0.375 are systematically studied by means of periodic density functional theory calculations for different compositions and arrangements. An analysis of the site preference for intercalation processes is carried out, while energy barriers for the diffusion paths have been computed in detail. Our results indicate that the Li insertion is thermodynamically favorable at octahedral sites 16c in the studied composition range, and Li migration from tetrahedral sites 8a to octahedral sites 16c stabilizes the structure and becomes favorable for compositions x 0.25. Diffusion paths from less stable arrangements involving Li migrations between tetrahedral and octahedral sites exhibit the lowest energy barrier since the corresponding trajectories and energy profiles take place across a triangle made by three neighboring oxygen anions without structural modification. Theoretical and experimental diffusion coefficients are in reasonable agreemen

    Neuroglial involvement in abnormal glutamate transport in the cochlear nuclei of the Igf1—/— mouse

    Full text link
    Insulin-like growth factor 1 (IGF-1) is a powerful regulator of synaptic activity and a deficit in this protein has a profound impact on neurotransmission, mostly on excitatory synapses in both the developing and mature auditory system. Adult Igf1—/— mice are animal models for the study of human syndromic deafness; they show altered cochlear projection patterns into abnormally developed auditory neurons along with impaired glutamate uptake in the cochlear nuclei, phenomena that probably reflect disruptions in neuronal circuits. To determine the cellular mechanisms that might be involved in regulating excitatory synaptic plasticity in 4-month-old Igf1—/— mice, modifications to neuroglia, astroglial glutamate transporters (GLTs) and metabotropic glutamate receptors (mGluRs) were assessed in the cochlear nuclei. The Igf1—/— mice show significant decreases in IBA1 (an ionized calcium-binding adapter) and glial fibrillary acidic protein (GFAP) mRNA expression and protein accumulation, as well as dampened mGluR expression in conjunction with enhanced glutamate transporter 1 (GLT1) expression. By contrast, no differences were observed in the expression of glutamate aspartate transporter (GLAST) between these Igf1—/— mice and their heterozygous or wildtype littermates. These observations suggest that congenital IGF-1 deficiency may lead to alterations in microglia and astrocytes, an upregulation of GLT1, and the downregulation of groups I, II and III mGluRs. Understanding the molecular, biochemical and morphological mechanisms underlying neuronal plasticity in a mouse model of hearing deficits will give us insight into new therapeutic strategies that could help to maintain or even improve residual hearing when human deafness is related to IGF-1 deficiencyThis work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO; SAF2016-788898-C2-1R) to JJ and VF-S; Seventh Framework Programme (FP7)-HEALTH- 2012-INNOVATON (#304925) to JJ; CIBERER/FEDER ACCI-ER16P5AC7091 and ER17P5AC7612 to LR-R; and Spanish MINECO/FEDER (SAF2014-53979-R), FP7- PEOPLE-2013-IAPP TARGEAR, CIBERER/FEDER (ACCIER16P5AC7091 and ER17P5AC7612) to IV-N. LR-R holds a contract supported by CIBERER (Institute of Health Carlos III) co-financed with FEDER fund

    Neuroglial Involvement in Abnormal Glutamate Transport in the Cochlear Nuclei of the Igf1−/− Mouse

    Get PDF
    Insulin-like growth factor 1 (IGF-1) is a powerful regulator of synaptic activity and a deficit in this protein has a profound impact on neurotransmission, mostly on excitatory synapses in both the developing and mature auditory system. Adult Igf1−/− mice are animal models for the study of human syndromic deafness; they show altered cochlear projection patterns into abnormally developed auditory neurons along with impaired glutamate uptake in the cochlear nuclei, phenomena that probably reflect disruptions in neuronal circuits. To determine the cellular mechanisms that might be involved in regulating excitatory synaptic plasticity in 4-month-old Igf1−/− mice, modifications to neuroglia, astroglial glutamate transporters (GLTs) and metabotropic glutamate receptors (mGluRs) were assessed in the cochlear nuclei. The Igf1−/− mice show significant decreases in IBA1 (an ionized calcium-binding adapter) and glial fibrillary acidic protein (GFAP) mRNA expression and protein accumulation, as well as dampened mGluR expression in conjunction with enhanced glutamate transporter 1 (GLT1) expression. By contrast, no differences were observed in the expression of glutamate aspartate transporter (GLAST) between these Igf1−/− mice and their heterozygous or wildtype littermates. These observations suggest that congenital IGF-1 deficiency may lead to alterations in microglia and astrocytes, an upregulation of GLT1, and the downregulation of groups I, II and III mGluRs. Understanding the molecular, biochemical and morphological mechanisms underlying neuronal plasticity in a mouse model of hearing deficits will give us insight into new therapeutic strategies that could help to maintain or even improve residual hearing when human deafness is related to IGF-1 deficiency

    Differences in colour gamut obtained with three synthetic red food colourants compared with three natural ones: pH and heat stability

    Get PDF
    The current trend in European markets towards natural ingredients has stimulated the interest in natural colourants. When it is decided to replace a colourant, normally a synthetic colourant with a natural one, it is interesting to know how the colour would be perceived, by locating their coordinates in the a*b*-diagram. The colours of three red natural colourants and three red synthetic ones have been compared. The natural colourants would be visually perceived as less intense than the synthetic colourants; this perception could be a signal of high quality as recognised and accepted by consumers. The hue (hab) of the natural colourants was red-bluish while the synthetic ones showed a red-orange character and they were located in a wider area of hue, having values apart from the rest, thus they could not be replaceable. The synthetic colourants showed less colour differences than the natural ones when subjected to pH variations and heat treatments.Comisión Interministerial de Ciencia y Tecnología AGL2009-12785-C02-0

    Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea.

    Get PDF
    Stress-activated protein kinases (SAPK) are associated with sensorineural hearing loss (SNHL) of multiple etiologies. Their activity is tightly regulated by dual-specificity phosphatase 1 (DUSP1), whose loss of function leads to sustained SAPK activation. Dusp1 gene knockout in mice accelerates SNHL progression and triggers inflammation, redox imbalance and hair cell (HC) death. To better understand the link between inflammation and redox imbalance, we analyzed the cochlear transcriptome in Dusp1-/- mice. RNA sequencing analysis (GSE176114) indicated that Dusp1-/- cochleae can be defined by a distinct profile of key cellular expression programs, including genes of the inflammatory response and glutathione (GSH) metabolism. To dissociate the two components, we treated Dusp1-/- mice with N-acetylcysteine, and hearing was followed-up longitudinally by auditory brainstem response recordings. A combination of immunofluorescence, Western blotting, enzymatic activity, GSH levels measurements and RT-qPCR techniques were used. N-acetylcysteine treatment delayed the onset of SNHL and mitigated cochlear damage, with fewer TUNEL+ HC and lower numbers of spiral ganglion neurons with p-H2AX foci. N-acetylcysteine not only improved the redox balance in Dusp1-/- mice but also inhibited cytokine production and reduced macrophage recruitment. Our data point to a critical role for DUSP1 in controlling the cross-talk between oxidative stress and inflammation

    A Comparative Study of Age-Related Hearing Loss in Wild Type and Insulin-Like Growth Factor I Deficient Mice

    Get PDF
    Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1−/− null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1+/+ and null Igf1−/− mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1−/− null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1+/+ wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1−/− null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or ameliorate age-related hearing loss
    corecore