Intensive research in the last decade shows that the prototypic angiogenic factor vascular endothelial growth factor (VEGF) can have direct effects in neurons and modulate processes such as neuronal ...migration, axon outgrowth, axon guidance and neuronal survival. Depending on the neuronal cell type and the process, VEGF seems to exert these effects by signaling via different receptors. It is also becoming clear that other VEGF ligands such as VEGF-B, -C and -D can act in various neuronal cell types as well. Moreover, apart from playing a role in physiological conditions, VEGF and VEGF-B have been related to different neurological disorders. We give an update on how VEGF controls different processes during neurodevelopment as well as on its role in several neurodegenerative disorders. We also discuss recent findings demonstrating that other VEGF ligands influence processes such as neurogenesis and dendrite arborization and participate in neurodegeneration.
Glutathione and mitochondria Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C
Frontiers in pharmacology,
07/2014, Volume:
5
Journal Article
Peer reviewed
Open access
Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and ...detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer's disease.
Brain function critically relies on blood vessels to supply oxygen and nutrients, to establish a barrier for neurotoxic substances, and to clear waste products. The archetypal vascular endothelial ...growth factor, VEGF, arose in evolution as a signal affecting neural cells, but was later co-opted by blood vessels to regulate vascular function. Consequently, VEGF represents an attractive target to modulate brain function at the neurovascular interface. On the one hand, VEGF is neuroprotective, through direct effects on neural cells and their progenitors and indirect effects on brain perfusion. In accordance, preclinical studies show beneficial effects of VEGF administration in neurodegenerative diseases, peripheral neuropathies and epilepsy. On the other hand, pathologically elevated VEGF levels enhance vessel permeability and leakage, and disrupt blood-brain barrier integrity, as in demyelinating diseases, for which blockade of VEGF may be beneficial. Here, we summarize current knowledge on the role and therapeutic potential of VEGF in neurological diseases.
Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose tissue ...dysfunction in obesity are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) and omental (OM) fat from lean subjects and obese individuals with different degrees of insulin sensitivity was performed to identify adipose tissue biomarkers related to obesity‐associated metabolic disease. Our results suggest that dysregulation of both adipose tissue extracellular matrix (ECM) organization and intracellular trafficking processes may be associated with IR in obesity. Thus, abnormal accumulation of the small leucine‐rich proteoglycan, lumican, as observed in SC fat of IR obese individuals, modifies collagen I organization, impairs adipogenesis and activates stress processes endoplasmic reticulum and oxidative stress in adipocytes. In OM fat, IR is associated with increased levels of the negative regulator of the Rab family of small GTPases, GDI2, which alters lipid storage in adipocytes by inhibiting insulin‐stimulated binding of the Rab protein, Rab18, to lipid droplets. Together, these results indicate that lumican and GDI2 might play depot‐dependent, pathogenic roles in obesity‐associated IR. Our findings provide novel insights into the differential maladaptive responses of SC and OM adipose tissue linking obesity to IR.
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•A comprehensive and critical review on the analysis of questioned documents is described.•Analysis of pen inks through a wide range of analytical techniques is discussed.•Most ...relevant articles on other samples related to questioned documents are reviewed.•Trends in the analysis of questioned documents are concluded.
During the last years (2000–2014), many publications concerning the forensic analysis of questioned documents have been published, and new techniques and methodologies are nowadays employed to overcome forensic caseworks. This article reviews a comprehensive collection of the works focused on this issue, including dating studies, the analysis of inks from pens and printers, the analysis of paper, the analysis of other samples related to questioned documents and studies on intersecting lines. These sections highlight the most relevant analytical studies by a wide range of analytical techniques. Separation and spectrometric techniques are critically discussed and compared, emphasizing the advantages and disadvantages of each one. Finally, concluding remarks on the research published are included.
Ultralong organic phosphorescence holds great promise as an important approach for optical materials and devices. Most of phosphorescent organic molecules with long lifetimes are substituted with ...heavy atoms or carbonyl groups to enhance the intersystem crossing (ISC), which requires complicated design and synthesis. Here, we report a cyclization-promoted phosphorescence phenomenon by boosting ISC. N-butyl carbazole exhibits a phosphorescence lifetime (τp) of only 1.45 ms and a low phosphorescence efficiency in the solution state at 77 K due to the lack of efficient ISC. In order to promote its phosphorescence behavior, we explored the influence of conjugation. By linear conjugation of four carbazole units, possible ISC channels are increased so that a longer τp of 2.24 s is observed. Moreover, by cyclization, the energy gap between the singlet and triplet states is dramatically decreased to 0.04 eV for excellent ISC efficiency accompanied by increased rigidification to synergistically suppress the nonradiative decay, resulting in satisfactory phosphorescence efficiency and a prolonged τp to 3.41 s in the absence of any heavy atom or carbonyl group, which may act as a strategy to prepare ultralong phosphorescent organic materials by enhancing the ISC and rigidification.
A comparative study of the optical properties of two well-known copolymers for photovoltaic applications, the PTB7 and the PTB7-Th, is presented. This study contributes to the understanding of the ...photophysics and permits correlation of the morphological change to the optical properties. For this purpose, Variable Angle Spectroscopic Ellipsometry (VASE) measurements are performed to determine the optical transitions as well as the band gap of PTB7 and PTB7-Th thin films from the imaginary parts of the dielectric functions. Then, the molecular aggregations in chlorobenzene solutions are investigated by means of absorbance and photoluminescence measurements as a function of concentration and temperature. These solution measurements are compared to film measurements in order to isolate interchain and intrachain optical transitions.
Inorganic oxidizing energetic salts including nitrates, chlorates and perchlorates are widely used in the manufacture of not only licit pyrotechnic compositions, but also illicit homemade explosive ...mixtures. Their identification in forensic laboratories is usually accomplished by either capillary electrophoresis or ion chromatography, with the disadvantage of dissociating the salt into its ions. On the contrary, vibrational spectroscopy, including IR and Raman, enables the non-invasive identification of the salt, i.e. avoiding its dissociation. This study focuses on the discrimination of all nitrate, chlorate and perchlorate salts that are commercially available, using both Raman and IR spectroscopy, with the aim of testing whether every salt can be unequivocally identified. Besides the visual spectra comparison by assigning every band with the corresponding molecular vibrational mode, a statistical analysis based on Pearson correlation was performed to ensure an objective identification, either using Raman, IR or both. Positively, 25 salts (out of 72) were unequivocally identified using Raman, 30 salts when using IR and 44 when combining both techniques. Negatively, some salts were undistinguishable even using both techniques demonstrating there are some salts that provide very similar Raman and IR spectra.
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•IR and Raman spectroscopy to identify nitrate, chlorate and perchlorate salts•IR and Raman spectral bands are mainly due to anion vibrations.•Small shifts in spectral bands (due to anions) are influenced by the cation.•Multivariate Pearson correlation is suitable to discriminate inorganic salts.•Some salts were undistinguishable even using both IR and Raman spectroscopy.
Perylene tetracarboxylic diimide (PTCDI) derivatives stand out as one of the most investigated families of air-stable n-type organic semiconductors for organic thin-film transistors. Here, we use ...density functional theory to illustrate how it is possible to control the charge-transport parameters of PTCDIs as a function of the type, number, and positions of the substituents. Specifically, two strategies of functionalization related to core and end substitutions are investigated. While end-substituted PTCDIs present the same functional molecular backbone, their molecular packing in the crystal significantly varies; as a consequence, this series of derivatives constitutes an ideal test bed to evaluate the models that describe charge-transport in organic semiconductors. Our results indicate that large bandwidths along with small effective masses can be obtained with the insertion of appropriate substituents on the nitrogens, in particular halogenated aromatic groups.
The nuclear translocation and activity of the cotranscriptional activators YAP and TAZ (YAP/TAZ) in endothelial cells (ECs) are crucial during developmental angiogenesis. Here, we studied the role of ...YAP/TAZ signaling in ECs in tumor angiogenesis and found that the expression of
and downstream target genes in ECs correlated with tumor vascularization in human colorectal carcinomas and skin melanoma. Treatment with the YAP/TAZ inhibitor verteporfin reduced vessel density and tumor progression in a mouse colorectal cancer (CRC) model. Conditional deletion of YAP/TAZ in ECs reduced tumor angiogenesis and growth in a mouse B16-F10 melanoma model. Using cultured ECs and mice with EC-specific ablation, we showed that signal transducer and activator of transcription 3 (STAT3) was required for the activation of YAP/TAZ in tumor-associated ECs. Moreover, we showed that STAT3-mediated signaling promoted YAP/TAZ activity and that the nuclear shuttling machinery for STAT3 was also required for YAP/TAZ nuclear translocation. Together, our data highlight the role of YAP/TAZ as critical players in ECs during tumor angiogenesis and provide insight into the signaling pathways leading to their activation.
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