Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti‐stress responses; these adaptations were fundamental forces during evolution. Central to anti‐stress responses are a number of short‐lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2‐related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in developmental lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics, the appearance of Diabetes Type 1 hallmarks and aging acceleration. Genetic or dietary suppression of Insulin/IGF‐like signaling (IIS) titrated Nrf2 activity to lower levels, largely normalized metabolic pathways signaling, and extended flies’ lifespan. Thus, prolonged stress signaling by otherwise cytoprotective short‐lived stress sensors perturbs IIS resulting in re‐allocation of resources from growth and longevity to somatic preservation and stress tolerance. These findings provide a reasonable explanation of why most (if not all) cytoprotective stress sensors are short‐lived proteins, and it also explains the build‐in negative feedback loops (shown here for Nrf2); the low basal levels of these proteins, and why their suppressors were favored by evolution.

Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3rd and 10th day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers.

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The synthesis and characterization of "2 + 1" complexes of the [M(CO)(3)](+) (M = Re, (99m)Tc) core with the β-diketones acetylacetone (complexes 2, 8) and curcumin (complexes 5, 10 and 6, 11) as bidentate OO ligands, and imidazole or isocyanocyclohexane as monodentate ligands is reported. The complexes were synthesized by reacting the [NEt(4)](2)[Re(CO)(3)Br(3)] precursor with the β-diketone to generate the intermediate aqua complex fac-Re(CO)(3)(OO)(H(2)O) that was isolated and characterized, followed by replacement of the labile water by the monodentate ligand. All complexes were characterized by mass spectrometry, NMR and IR spectroscopies, and elemental analysis. In the case of complex 2, bearing imidazole as the monodentate ligand, X-ray analysis was possible. The chemistry was successfully transferred at (99m)Tc tracer level. The curcumin complexes 5 and 6, as well as their intermediate aqua complex 4, that bear potential for radiopharmaceutical applications due to the wide spectrum of pharmacological activity of curcumin, were successfully tested for selective staining of β-amyloid plaques of Alzheimer's disease. The fact that the complexes maintain the affinity of the mother compound curcumin for β-amyloid plaques prompts for further exploration of their chemistry and biological properties as radioimaging probes.

The in vitro utilization of biocompatible ferromagnetic nanoparticles (BFNs) in hemodialysis (HD), routinely used today for the treatment of end stage renal disease (ESRD), is introduced in this work. The proposed strategy is termed magnetically assisted hemodialysis (MAHD) and it aims to become a more efficient development of conventional HD. The method is based on the production of biocompatible ferromagnetic nanoparticles-targeted binding substances conjugates (BFNs-TBSs Cs) constructed of BFNs and specifically designed TBSs that should have high affinity and binding capacity for target toxic substances (TTSs) which must be removed from the ESRD patient subjected to HD. Antibodies or even specific proteins could serve as the TBS of the desired BFNs-TBSs Cs. The BFNs-TBSs Cs should be administered to the patient timely prior to the MAHD session so as to bind with the desired TTSs during their free circulation in the vascular network. Eventually, the complete BFNs-TBSs-TTSs structure can be selectively removed during the MAHD session by means of an external inhomogeneous magnetic field that is applied either at the dialyzer or at other collection point(s) along the blood circulation line of the dialysis machine. The advantages of MAHD over conventional HD regarding the patient's comfort and overall health status are discussed in detail among practical issues. To examine this proposition we employed Fe(3)O(4) and bovine serum albumin (BSA) as the BFN and the TBS constituents respectively, since they are both highly biocompatible. By means of x-ray diffraction, atomic force microscopy, circular dichroism spectropolarimetry, UV-vis spectrophotometry, SQUID magnetometry, and nuclear magnetic resonance we evaluated (i) the structural/morphological characteristics, (ii) the magnetic retraction efficiency, and most importantly (iii) the toxin binding affinity and capacity of both bare Fe(3)O(4) BFNs and Fe(3)O(4)-BSA Cs by performing in vitro experiments on specific TTSs. Homocysteine and p-cresol were chosen as representative TTSs and were investigated in great detail. The results obtained prove the in vitro applicability of the proposed MAHD method. Corrections were made to this article on 6 November 2007 (see figure 10 caption and lines 10 and 11 of page 11). The corrected electronic version is identical to the print version.

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The discovery of new active natural products is hampered by laborious purification processes that often end up to the re-isolation of known compounds. We demonstrate here that, spectral data reflecting concentration fluctuations of components can correlate statistically with measurable dose-dependent properties on the basis of a Heterocovariance approach deconvoluting the active components structure. Variance of extract constituents was achieved through statistically meaningful collections of plants from different families, genus, and species. This fluctuation was also obtained through the fractionation of a single plant extract by separation techniques. The NMR and HRMS spectra of the extracts and fractions were recorded, as well as their ability to inhibit tyrosinase or 5-lipoxygenase enzymes. Biological activity was statistically correlated with spectral data deciphering the active compounds through the Heterocovariance approach prior to any purification. Natural products (NPs) possess significant and well-documented biological properties representing a bioactivity hotspot in the chemical space. [1] However, the great majority of existing chemodiversity remains still unexplored as only a minute fraction of biodiversity has been chemically characterised. [2] The complexity of plant extracts in terms of number, concentration levels and nature of contained metabolites renders this goal rather challenging. Traditional isolation and scale-up proce-dures are inefficient and often become a bottleneck resulting to the constant re-isolation and re-identification of known compounds. Thus, dereplication methods have been emerged aiming to accelerate and rationalize the entire discovery process. [3] Recently, there is a considerable interest by the NP scientific community to adopt metabolomics approaches introducing a more holistic concept in the analysis of complex mixtures. [4][5][6] Metabolomics have found several applications in the area of NPs by means of metabolic profiling and fingerprinting. [7][8][9] They have been successfully employed for chemotaxonomic studies exploring the proximity of different plant species, origins or organs in respect to their metabolite profile. [10] Interestingly, different metabolomics studies have contributed significantly in the quality assessment of botanical preparations enabling the monitoring of the metabolome composition. [11,12] Metabolomics studies are based on the combined application of spectroscopic techniques and multivariate statistical approaches. [13] Among these lines, specific statistical methods for the analysis of the complex spectroscopic data were developed in order to identify components of a complex mixture. The statistical total correlation spectroscopy (STOCSY) [14] can detect multiple NMR peaks from the same molecule based on their intensities multi-colinearity in a set of NMR spectra. Moreover, correlation can be achieved between MS and NMR data in statistical heterospectroscopy (SHY). [15] It has been reported recently a new approach based on MS and activit...