The yeast hnRNP-Like proteins Yra1p and Yra2p participate in mRNA export through interaction with Mex67p

Yra1p is an essential nuclear protein which belongs to the evolutionarily conserved REF (RNA and export factor binding proteins) family of hnRNP-like proteins. Yra1p contributes to mRNA export in vivo and directly interacts with RNA and the shuttling mRNP export receptor Mex67p in vitro. Here we describe a second nonessential Saccharomyces cerevisiae family member, called Yra2p, which is able to complement a YRA1 deletion when overexpressed. Like other REF proteins, Yra1p and Yra2p consist of two highly conserved N- and C-terminal boxes and a central RNP-like RNA-binding domain (RBD). These conserved regions are separated by two more variable regions, N-vr and C-vr. Surprisingly, the deletion of a single conserved box or the deletion of the RBD in Yra1p does not affect viability. Consistently, neither the conserved N and C boxes nor the RBD is required for Mex67p and RNA binding in vitro. Instead, the N-vr and C-vr regions both interact with Mex67p and RNA. We further show that Yra1 deletion mutants which poorly interact with Mex67p in vitro affect the association of Mex67p with mRNP complexes in vivo and are paralleled by poly(A)(+) RNA export defects. These observations support the idea that Yra1p promotes mRNA export by facilitating the recruitment of Mex67p to the mRNP.     

Description of Crassolabium persicum sp. n. (Nematoda, Dorylaimida, Qudsianematidae), an interesting species from Iran

A new species of the genus Crassolabium, Crassolabium persicumsp. n., collected from Arasbaran rangelands of Iran, is described and illustrated. It is characterized by its body 1.92-2.40 mm long, lip region offset by constriction and 17-19 μm wide, odontostyle 16-19 μm long with aperture occupying less than one-third (27-30%) its length, neck 428-690 μm long, pharyngeal expansion 369-390 μm long or occupying 54-56% of total neck length, female genital system amphidelphic, uterus bipartite and 162-218 μm long or 2.3-3.5 times as long as body diameter, pars refringens vaginae well developed, V = 54-57.5, vulva longitudinal, prerectum bearing a blind sac, tail conical with rounded tip to conoid (25-36 μm, c=60-69, c'=0.5-0.9), spicules 68-72 μm long, precloacal pair of supplements far (22-27 μm) from cloacal aperture, and 13-17 shortly spaced ventromedian supplements with hiatus. The new taxon is compared in depth to its relatives in Crassolabium as well as other similar species of Aporcelaimellus and Amblydorylaimus.     

Isotactic polypropylene biodegradation by a microbial community: physicochemical characterization of metabolites produced.

From a selective enrichment culture prepared with different soil samples on starch-containing polyethylene we isolated four microaerophilic microbial communities able to grow on this kind of plastic with no additional carbon source. One consortium, designated community 3S, was tested with pure isotactic polypropylene to determine whether the consortium was able to degrade this polymer. Polypropylene strips were incubated for 5 months in a mineral medium containing sodium lactate and glucose in screw-cap bottles. Dichloromethane crude extracts of the cultures revealed that the weight of extracted materials increased with incubation time, while the polypropylene sample weight decreased. The extracted materials were characterized by performing chromatographic and spectral analyses (thin-layer chromatography, liquid chromatography, gas chromatography-mass spectrometry, infrared spectrometry, nuclear magnetic resonance). Three main fractions were detected and analyzed; a mixture of hydrocarbons at different degrees of functionalization was found together with a mixture of aromatic esters, as the plasticizers usually added to polyolefinic structures.     

The peptide nucleic acid targeted to a regulatory sequence of the translocated c-myc oncogene in Burkitt's lymphoma lacks immunogenicity: follow-up characterization of PNAEmu-NLS

The present study aims to evaluate the antigenicity of a PNA complementary to the Emu sequence (PNAEmu) with cancer therapeutic potential properties in Burkitt's lymphoma (BL). In BL cells, the c-myc oncogene is repositioned next to the Emu enhancer of the immunoglobulin (Ig) locus, due to chromosomal translocation, and up-regulated. PNAEmu linked to a nuclear localization signal peptide was shown specifically to block c-myc hyperexpression by inhibiting cell growth in vitro and in vivo. Recently, we reported that the administration of PNAEmu to mice, following inoculation with BL cells, hinders tumor growth without toxic effects. To investigate the potential use of PNAEmu in clinical applications further, we tested its antigenicity. Mice were inoculated with an emulsion of free PNA or PNA crosslinked to the immunogenic carrier keyhole limpet hemocyanin (KLH) with Freund's adjuvant. Antibodies to free PNA were undetected, whereas both IgG and IgM antibodies to PNA-KLH were detected in mouse serum 28 and 38 days after inoculation.     

Synthesis of novel antimitotic agents based on 2-amino-3-aroyl-5-(hetero)arylethynyl thiophene derivatives

Microtubules are dynamic structures that play a crucial role in cellular division and are recognized as an important target for cancer therapy. In search of new compounds with strong antiproliferative activity and simple molecular structure, a new series of 2-amino-3-(3′,4′,5′-trimethoxybenzoyl)-5-(hetero)aryl ethynyl thiophene derivatives was prepared by the Sonogashira coupling reaction of the corresponding 5-bromothiophenes with several (hetero)aryl acetylenes. When these compounds were analyzed in vitro for their inhibition of cell proliferation, the 2- and 3-thiophenyl acetylene derivatives were the most powerful compounds, both of which exerted cytostatic effects at submicromolar concentrations. In contrast, the presence of a more flexible ethyl chain between the (hetero)aryl and the 5-position of the thiophene ring resulted in significant reduction in activity relative to the 5-(hetero)aryl acetylene substituted derivatives. The effects of a selected series of compounds on cell cycle progression correlated well with their strong antiproliferative activity and inhibition of tubulin polymerization. We found that the antiproliferative effects of the most active compounds were associated with increase of the proportion of cells in the G₂/M and sub-G₁ phases of the cell cycle.     

Biliary lithiasis in early pregnancy and abnormal development of facial and distal limb bones (Binder syndrome): a possible role for vitamin K deficiency

BACKGROUND: Binder syndrome is a maxillonasal dysostosis characterized by midface and nasal hypoplasia, sometimes associated with short terminal phalanges of fingers and toes and transient radiological features of chondrodysplasia punctata. Warfarin- or phenytoin-induced vitamin K deficiency during early pregnancy is a well-established etiology for this syndrome, which occurs nevertheless sporadically in most cases. CASE(S): We describe here the first case, to our knowledge, of Binder syndrome in a child whose mother presented with biliary lithiasis in early pregnancy. The mother proved to have a decrease in clotting factors II, VII, and X, and in prothrombin time, at 11 weeks of gestation, which was highly suggestive of vitamin K deficiency. CONCLUSIONS: The biliary lithiasis-induced vitamin K deficiency in early pregnancy is likely to have resulted in Binder syndrome. This observation should prompt physicians to carefully check for vitamin K deficiency in pregnant women presenting with biliary lithiasis, in order to prevent Binder syndrome in the fetus by providing intravenous vitamin K supplementation as soon as possible. Finally, reassuring genetic counseling regarding the genetic risk for future pregnancies is to be provided to the parents.     

Molecular characterization of cytotoxic and resistance mechanisms induced by NCX 4040, a novel NO-NSAID, in pancreatic cancer cell lines*

Although non steroidal antiinflammatory drugs (NSAIDs) have been shown to be effective as chemopreventive agents, important side-effects limit their clinical use. A promising novel class of drugs, nitric oxide-donating NSAIDs (NO-NSAIDs), has been found to be more active than classical NSAIDs. This study explored the effect of the NO-donating aspirin derivative, NCX 4040, on three human pancreatic adenocarcinoma cell lines (Capan-2, MIA PaCa-2 and T3M4). NCX 4040 activity was compared with that of NCX 4016 (an NO₂-positional isomer of NCX 4040), SNAP (a standard NO-releasing molecule), NCX 4042 (denitrated analog of NCX 4040), and aspirin. NCX 4040 showed a striking cytocidal activity in all cell lines, already inducing significant percentages of apoptotic cells at 10 μM in Capan-2 cell lines. This study focused on the biological mechanisms of sensitivity and resistance to NCX 4040, highlighting that the cytotoxic action of this drug may be due to the hyperexpression of Bax, its translocation to the mitochondria, the release of Cytochrome C, and the activation of caspases-9 and -3, overall in a p53-independent manner. Moreover, the use of a specific COX-2 inhibitor (NS 398) in the experimental models showed that COX-2 hyperexpression could partially explain the resistance mechanisms to NCX 4040. This study was supported by Istituto Oncologico Romagnolo, Forlì, and by the Italian, Ministry of Health, 2004.