Semi-synthetic aristolactams—inhibitors of CDK2 enzyme

Several analogs of aristolochic acids were isolated and derivatized into their lactam derivatives to study their inhibition in CDK2 assay. The study helped to derive some conclusions about the structure–activity relation around the phenanthrin moiety. Semi-synthetic aristolactam 21 showed good activity with inhibition IC₅₀ of 35 nM in CDK2 assay. The activity of this compound was comparable to some of the most potent synthetic compounds reported in the literature.     

Diversity of ndo genes in mangrove sediments exposed to different sources of polycyclic aromatic hydrocarbon pollution

Polycyclic aromatic hydrocarbon (PAH) pollutants originating from oil spills and wood and fuel combustion are pollutants which are among the major threats to mangrove ecosystems. In this study, the composition and relative abundance in the sediment bacterial communities of naphthalene dioxygenase (ndo) genes which are important for bacterial adaptation to environmental PAH contamination were investigated. Three urban mangrove sites which had characteristic compositions and levels of PAH compounds in the sediments were selected. The diversity and relative abundance of ndo genes in total community DNA were assessed by a newly developed ndo denaturing gradient gel electrophoresis (DGGE) approach and by PCR amplification with primers targeting ndo genes with subsequent Southern blot hybridization analyses. Bacterial populations inhabiting sediments of urban mangroves under the impact of different sources of PAH contamination harbor distinct ndo genotypes. Sequencing of cloned ndo amplicons comigrating with dominant DGGE bands revealed new ndo genotypes. PCR-Southern blot analysis and ndo DGGE showed that the frequently studied nah and phn genotypes were not detected as dominant ndo types in the mangrove sediments. However, ndo genotypes related to nagAc-like genes were detected, but only in oil-contaminated mangrove sediments. The long-term impact of PAH contamination, together with the specific environmental conditions at each site, may have affected the abundance and diversity of ndo genes in sediments of urban mangroves.     

Street heroin induces mitochondrial dysfunction and apoptosis in rat cortical neurons

Cortical function has been suggested to be highly compromised by repeated heroin self-administration. We have previously shown that street heroin induces apoptosis in neuronal-like PC12 cells. Thus, we analysed the apoptotic pathways involved in street heroin neurotoxicity using primary cultures of rat cortical neurons. Our street heroin sample was shown to be mainly composed by heroin, 6-monoacetylmorphine and morphine. Exposure of cortical neurons to street heroin induced a slight decrease in metabolic viability, without loss of neuronal integrity. Early activation of caspases involved in the mitochondrial apoptotic pathway was observed, culminating in caspase 3 activation, Poly-ADP Ribose Polymerase (PARP) cleavage and DNA fragmentation. Apoptotic morphology was completely prevented by the non-selective caspase inhibitor z-VAD-fmk, indicating an important role for caspases in neurodegeneration induced by street heroin. Ionotropic glutamate receptors, opioid receptors and oxidative stress were not involved in caspase 3 activation. Interestingly, street heroin cytotoxicity was shown to be independent of a functional mitochondrial respiratory chain, as determined using NT-2 rho(0) cells. Nonetheless, in street heroin-treated cortical neurons, cytochrome c was released, accompanied by a decrease in mitochondrial potential and Bcl-2/Bax. Pure heroin hydrochloride similarly decreased metabolic viability but only slightly activated caspase 3. Altogether, our data suggest an important role for mitochondria in mediating street heroin neurotoxic effects.     

Microbiological quality of water and dialysate in a haemodialysis unit in Ponta Grossa-PR, Brazil

AIMS: The objective of the study was to determine the microbiological quality of samples of water and dialysate in a haemodialysis unit. METHODS AND RESULTS: Seventy-two samples each of water and dialysate were collected during November 2003 to April 2004. The following microbiological analyses were performed: test for total and faecal coliforms, which produced negative results for all the samples; counts of total heterotrophic bacteria, where three samples of water and two of dialysate showed levels higher than those permitted by national standards; and endotoxin assay, which revealed high quantities only in samples of water that preceded reverse osmosis. Nonfermenting Gram-negative bacteria were identified in 54 samples of dialysate and in 26 samples of water. The test for adhesion to an inert surface showed that various bacteria were capable of forming biofilms. Twenty-seven per cent of the bacteria were resistant to sodium hypochlorite at 500 ppm for 10-min contact time. Sixty per cent of the isolates were resistant to three or more antibiotics. CONCLUSIONS: Water and dialysate can be a source of infection for patients who need haemodialysis. SIGNIFICANCE AND IMPACT OF THE STUDY: An adequate system for water treatment, disinfection of the haemodialysis system and microbiological monitoring of the water and dialysate are necessary to reduce bacteraemia and pyrogenia outbreaks.     

Cloning and Biochemical Characterization of <Emphasis Type="Italic">ToFZY</Emphasis>, a Tomato Gene Encoding a Flavin Monooxygenase Involved in a Tryptophan-dependent Auxin Biosynthesis Pathway

Indole-3-acetic acid (IAA), the main endogenous auxin, has been known for decades to be a key regulator for plant growth and development. Multiple routes have been proposed for IAA biosynthesis but physiologic roles or relevance of the different routes are still unclear. Recently, four members of the Arabidopsis thaliana YUC gene family have been implicated in an additional requirement of IAA involved in floral organ and vascular tissue formation. The loss-of-function yuc1yuc4 double mutants in Arabidopsis displayed phenotypes similar to the previously described loss-of-function floozy mutants in petunia (fzy). Moreover, it has been demonstrated that YUC1 encodes a flavin monooxygenase (FMO) that catalyzes a rate-limiting step of a tryptophan-dependent auxin biosynthesis pathway: the conversion of tryptamine to N-hydroxyl-tryptamine. Here we report on the genetic study of ToFZY, the putative tomato ortholog of YUC4 and FZY, including gene and cDNA sequence comparison and a preliminary expression analysis. In addition, we describe a novel conserved amino acid motif that may be considered a hallmark potentially useful for the identification of new YUC-like FMOs. We also demonstrate that ToFZY encodes a protein with the same enzymatic activity as YUC1. Finally, we provide evidence suggesting that the ToFZY gene belongs to a multigenic family whose members may exhibit a temporal and spatial specialization similar to that described in A. thaliana.     

Higher frequency of legitimate pollinators and fruit set of autotetraploid trees of Libidibia ferrea (Leguminosae) compared to diploids in a mixed tropical urban population

Journal of Plant Research - In mixed-ploidy populations, newly formed polyploids initially occur at low frequencies when compared to diploids. However, polyploidy may lead to morphological and...     

Effects of Ethanolic Extract of Cynara cardunculus (Artichoke) Leaves on Neuroinflammatory and Neurochemical Parameters in a Diet-Induced Mice Obesity Model

Neurochemical Research - This study aimed to evaluate the effect of Cynara cardunculus leaf ethanol extract on inflammatory and oxidative stress parameters in the hypothalamus, prefrontal cortex,...