Structure–Activity Relationship Analysis of the Peptide Deformylase Inhibitor 5‐Bromo‐1H‐indole‐3‐acetohydroxamic Acid

SAR by NMR : A series of indole compounds derived from 5‐bromo‐1H‐indole‐3‐acetohydroxamic acid were synthesized. Their inhibitory activities were evaluated against purified peptide deformylases (PDFs), and their antibacterial activities against B. subtilis, E. coli (wild type and tolC), and a variety of pathogens were also determined. The potency of the best inhibitors was related to the NMR footprints of the respective acids with ¹⁵N‐labeled E. coli Ni‐PDF.

     

Bioactive phytonutrients (omega fatty acids,tocopherols, polyphenols), in vitro inhibition of nitric oxide production and free radical scavenging activity of non-cultivated Mediterranean vegetables

Hydroalcoholic extracts from 18 non-cultivated vegetables traditionally consumed in Southern Italy were tested for their free radical scavenging activity (FRSA) in the DPPH (1,1-diphenyl-2-picrylhydrazil radical) screening assay and for their in vitro inhibition of nitric oxide (NO) production. The strongest activity was shown for Rubus caesius (leaves), Mentha spicata subsp. glabra (leaves) and Origanum vulgare subsp. viridulum (stems and leaves) with IC₅₀ values of 5, 6, 8 μg/ml, respectively. Extracts from non-cultivated Foeniculum vulgare subsp. piperitum (seeds), Amaranthus retroflexus (leaves) and M. spicata subsp. glabra (leaves) showed high in vitro inhibition of nitric oxide production, with an activity comparable to a reference drug, indomethacin. A significant cytotoxic effect was shown for the seeds of F. vulgare subsp. piperitum. A. retroflexus (leaves) presented the highest content in linoleic acid. R. caesius and M. spicata subsp. glabra had relatively high polyphenols content, 482 and 334 mg/g of extract, respectively.     

Influence of aeration and sludge retention time on ammonium oxidation to nitrite and nitrate

Partial nitrification to nitrite was reported to be technically feasible and economically favourable, especially when wastewater with high ammonium concentrations or low C/N ratios are treated. Nitritation can be obtained by selectively inhibiting nitrite oxidizing microrganisms through appropriate regulation of the system's pH, temperature, and sludge retention time. In addition to already known methods, the work showed that aeration patterns may play a relevant role too. Nitrification tests were performed in two lab-scale reactors operated under continuous and intermittent aeration, respectively. In both plants, temperature was maintained at 32 degrees C and pH was regulated at 7.2 by providing external buffer capacity when needed. The results showed that partial nitrification to nitrite was steadily obtained under oxygen limitation, independent of the sludge age. Therefore, the aeration pattern is proposed as an alternative parameter to the sludge retention time for controlling ammonium oxidation to nitrite.     

Passive standoff detection of chemical warfare agents on surfaces

Results are presented on the passive standoff detection and identification of chemical warfare (CW) liquid agents on surfaces by the Fourier-transform IR radiometry. This study was performed during surface contamination trials at Defence Research and Development Canada-Suffield in September 2002. The goal was to verify that passive long-wave IR spectrometric sensors can potentially remotely detect surfaces contaminated with CW agents. The passive sensor, the Compact Atmospheric Sounding Interferometer, was used in the trial to obtain laboratory and field measurements of CW liquid agents, HD and VX. The agents were applied to high-reflectivity surfaces of aluminum, low-reflectivity surfaces of Mylar, and several other materials including an armored personnel carrier. The field measurements were obtained at a standoff distance of 60 m from the target surfaces. Results indicate that liquid contaminant agents deposited on high-reflectivity surfaces can be detected, identified, and possibly quantified with passive sensors. For low-reflectivity surfaces the presence of the contaminants can usually be detected; however, their identification based on simple correlations with the absorption spectrum of the pure contaminant is not possible.     

Human Genetic Diseases Linked to the Absence of NEMO: An Obligatory Somatic Mosaic Disorder in Male

De novo somatic mutations are well documented in diseases such as neoplasia but are rarely reported in rare diseases. Hovewer, severe genetic diseases that are not compatible with embryonic development are caused exclusively by deleterious mutations that could only be found as mosaic and not as inherited mutations. We will review here the paradigmatic case of Incontinentia Pigmenti, a rare X-linked dominant disease caused by deficiency of the NEMO (also called IKKgamma) protein, which plays a pivotal role in tissue homeostasis. The loss-of-function mutations of NEMO are embryonically lethal in males while females survive because of unbalanced X-inactivation due to NEMO wild type (WT) expressing cells survival despite of NEMO mutant expressing cells. The few surviving IP males are obligatory mosaic mutants with the typical clinical presentation of IP in female. Indeed, the IP pathogenesis in the female and most likely also in the male somatic mosaics is based on the cellular effects of an impaired NEMO activity, but in the context of the interaction of genetically different cells in the affected tissue, which might underline the inflammatory status.     

Synuclein Analysis in Adult Xenopus laevis

The α-, β- and γ-synucleins are small soluble proteins expressed in the nervous system of mammals and evolutionary conserved in vertebrates. After being discovered in the cartilaginous fish Torpedo californica, synucleins have been sequenced in all vertebrates, showing differences in the number of genes and splicing isoforms in different taxa. Although α-, β- and γ-synucleins share high homology in the N-terminal sequence, suggesting their evolution from a common ancestor, the three isoforms also differ in molecular characteristics, expression levels and tissue distribution. Moreover, their functions have yet to be fully understood. Great scientific interest on synucleins mainly derives from the involvement of α-synuclein in human neurodegenerative diseases, collectively named synucleinopathies, which involve the accumulation of amyloidogenic α-synuclein inclusions in neurons and glia cells. Studies on synucleinopathies can take advantage of the development of new vertebrate models other than mammals. Moreover, synuclein expression in non-mammalian vertebrates contribute to clarify the physiological role of these proteins in the evolutionary perspective. In this paper, gene expression levels of α-, β- and γ-synucleins have been analysed in the main organs of adult Xenopus laevis by qRT-PCR. Moreover, recombinant α-, β- and γ-synucleins were produced to test the specificity of commercial antibodies against α-synuclein used in Western blot and immunohistochemistry. Finally, the secondary structure of Xenopus synucleins was evaluated by circular dichroism analysis. Results indicate Xenopus as a good model for studying synucleinopathies, and provide a useful background for future studies on synuclein functions and their evolution in vertebrates.     

Toxicity of Vanadium during Development of Sea Urchin Embryos: Bioaccumulation,Calcium Depletion,ERK Modulation and Cell-Selective Apoptosis

Vanadium toxicology is a topic of considerable importance as this metal is widely used in industrial and biomedical fields. However, it represents a potential emerging environmental pollutant because wastewater treatment plants do not adequately remove metal compounds that are subsequently released into the environment. Vanadium applications are limited due to its toxicity, so it is urgent to define this aspect. This metal is associated with sea urchin embryo toxicity as it perturbs embryogenesis and skeletogenesis, triggering several stress responses. Here we investigated its bioaccumulation and the correlation with cellular and molecular developmental pathways. We used cytotoxic concentrations of 1 mM and 500 μM to perform quantitative analyses, showing that vanadium accumulation interferes with calcium uptake during sea urchin development and provokes a disruption in the biomineralization process. At the end of the whole treatment, the accumulation of vanadium was about 14 and 8 μg for embryos treated respectively with 1 mM and 500 μM, showing a dose-dependent response. Then, we monitored the cell signaling perturbation, analyzing key molecular markers of cell survival/cell death mechanisms and the DNA fragmentation associated with apoptosis. This paper clarifies vanadium’s trend to accumulate directly into embryonic cells, interfering with calcium uptake. In addition, our results indicate that vanadium can modulate the ERK pathway and activate a cell-selective apoptosis. These results endorse the sea urchin embryo as an adequate experimental model to study metal-related cellular/molecular responses.