Interleukin-1beta and glutamate activate the NF-kappaB/Rel binding site from the regulatory region of the Amyloid Precursor Protein gene in primary neuronal cultures

We originally reported that members of the family of transcription factors NF-kappaB/Rel can specifically recognize two identical sequences, referred to as APPkappaB sites, which are present in the 5'-regulatory region of the APP gene. Here we show that the APPkappaB sites interact specifically with a complex which contains one of the subunits of the family, defined as p50 protein, and that they act as positive modulators of gene transcription in cells of neural origin. Additionally, the nuclear complex specifically binding to the APPkappaB sites is constitutively expressed in primary neurons from rat cerebellum and it is up-regulated in response to both the inflammatory cytokine interleukin-1beta (IL-1beta) and the excitatory amino acid glutamate. Since IL-1, whose levels are known to be induced in brain of individuals affected by Alzheimer's disease, and glutamate, are stimuli which have been regarded as major actors on the stage of neurodegenerative processes, we believe our evidence as potentially relevant for understanding the neuropathology associated with Alzheimer's disease

Nerve growth factor and bromocriptine: a sequential therapy for human bromocriptine-resistant prolactinomas.

Nerve growth factor (NGF) administration to athymic mice with transplanted human bromocriptine-resistant prolactinoma, results in the expression of dopamine D-2 receptors in the tumour and restores sensitivity to subsequent treatment with bromocriptine, which then produces normalisation of plasma prolactin and tumour regression. Sequential administration of NGF and bromocriptine thus may be a promising therapy for patients refractory to bromocriptine

Third-order nonlinear optical properties of stacked bacteriochlorophylls in bacterial photosynthetic light-harvesting proteins

Enhancement of the nonresonant second order molecular hyperpolarizabilities {gamma} were observed in stacked macrocyclic molecular systems, previously in a {micro}-oxo silicon phthalocyanine (SiPcO) monomer, dimer and trimer series, and now in bacteriochlorophyll a (BChla) arrays of light harvesting (LH) proteins. Compared to monomeric BChla in a tetrahydrofuran (THF) solution, the <{gamma}> for each macrocycle was enhanced in naturally occurring stacked macrocyclic molecular systems in the bacterial photosynthetic LH proteins where BChla`s are arranged in tilted face-to-face arrays. In addition, the {gamma} enhancement is more significant in B875 of LH1 than in B850 in LH2. Theoretical modeling of the nonresonant {gamma} enhancement using simplified molecular orbitals for model SiPcO indicated that the energy level of the two photon state is crucial to the {gamma} enhancement when a two photon process is involved, whereas the charge transfer between the monomers is largely responsible when one photon near resonant process is involved. The calculated results can be extended to {gamma} enhancement in B875 and B850 arrays, suggesting that BChla in B875 are more strongly coupled than in B850. In addition, a 50--160 fold increase in <{gamma}> for the S{sub 1} excited state of relative to S{sub 0} of bacteriochlorophyll in vivo was observed which provides an alternative method for probing excited state dynamics and a potential application for molecular switching

Recurrence of the oxazole motif in tubulin colchicine site inhibitors with anti-tumor activity

Because of its wide spectrum of targets and biological activities, the oxazole ring is a valuable heterocyclic scaffold in the design of new therapeutic agents with anticancer, antiviral, antibacterial, anti-inflammatory, neuroprotective, antidiabetic and antidepressant properties. The presence of two heteroatoms, oxygen and nitrogen, offers possible interactions (hydrogen, hydrophobic, van der Waals or dipoles bonds) with a broad range of receptors and enzymes. Furthermore, the oxazole core conjugates low cytotoxicity with improved compound solubility and is well suited to structural modifications such as substitution with different groups and condensation to aromatic, heteroaromatic or non-aromatic rings, offering diversity when introduced into scaffolds. These features make it a very attractive nucleus in medicinal chemistry. Herein we present a diverse array of oxazole derivatives with potential therapeutic use in multiple tumor models. The emphasis has been addressed to compounds with anti-tubulin activity reported in literature in the last decade, describing their structural features, efficiency and future perspectives

PTR-ToF-MS for the online monitoring of alcoholic fermentation in wine: assessment of VOCs variability associated with different combinations of Saccharomyces/non-Saccharomyces as a case-study

7openInternationalItalian coauthor/editorThe management of the alcoholic fermentation (AF) in wine is crucial to shaping product quality. Numerous variables (e.g., grape varieties, yeast species/strains, technological parameters) can affect the performances of this fermentative bioprocess. The fact that these variables are often interdependent, with a high degree of interaction, leads to a huge ‘oenological space’ associated with AF that scientists and professionals have explored to obtain the desired quality standards in wine and to promote innovation. This challenge explains the high interest in approaches tested to monitor this bioprocess including those using volatile organic compounds (VOCs) as target molecules. Among direct injection mass spectrometry approaches, no study has proposed an untargeted online investigation of the diversity of volatiles associated with the wine headspace. This communication proposed the first application of proton-transfer reaction-mass spectrometry coupled to a time-of-flight mass analyzer (PTR-ToF-MS) to follow the progress of AF and evaluate the impact of the different variables of wine quality. As a case study, the assessment of VOC variability associated with different combinations of Saccharomyces/non-Saccharomyces was selected. The different combinations of microbial resources in wine are among the main factors susceptible to influencing the content of VOCs associated with the wine headspaces. In particular, this investigation explored the effect of multiple combinations of two Saccharomyces strains and two non-Saccharomyces strains (belonging to the species Metschnikowia pulcherrima and Torulaspora delbrueckii) on the content of VOCs in wine, inoculated both in commercial grape juice and fresh grape must. The results demonstrated the possible exploitation of non-invasive PTR-ToF-MS monitoring to explore, using VOCs as biomarkers, (i) the huge number of variables influencing AF in wine, and (ii) applications of single/mixed starter cultures in wine. Reported preliminary findings underlined the presence of different behaviors on grape juice and on must, respectively, and confirmed differences among the single yeast strains ‘volatomes’. It was one of the first studies to include the simultaneous inoculation on two non-Saccharomyces species together with a S. cerevisiae strain in terms of VOC contribution. Among the other outcomes, evidence suggests that the addition of M. pulcherrima to the coupled S. cerevisiae/T. delbrueckii can modify the global release of volatiles as a function of the characteristics of the fermented matrixopenBerbegal, C.; Khomenko, I.; Russo, P.; Spano, G.; Fragasso, M.; Biasioli, F.; Capozzi, V.Berbegal, C.; Khomenko, I.; Russo, P.; Spano, G.; Fragasso, M.; Biasioli, F.; Capozzi, V

Excitonic Strings in one dimensional organic compounds

Important questions concern the existence of excitonic strings in organic compounds and their signatures in the photophysics of these systems. A model in terms of Hard Core Bosons is proposed to study this problem in one dimension. Mainly the cases with two and three particles are studied for finite and infinite lattices, where analytical results are accessible. It is shown that if bi-excitonic states exist, three-excitonic and even, n-excitonic strings, at least in a certain range of parameters, will exist. Moreover, the behaviour of the transitions from one exciton to the biexciton is fully clarified. The results are in agreement with exact finite cluster diagonalizations of several model Hamiltonians.Comment: 36 pages, 4 eps figs. to appear in Phys. Rev.