Vanadium(V) complexes with salicylaldehyde semicarbazone derivatives bearing in vitro anti-tumor activity toward kidney tumor cells (TK-10): crystal structure of [VVO2(5-bromosalicylaldehyde semicarbazone)

As a contribution to the development of novel vanadium complexes with pharmacologically interesting moieties, new dioxovanadium(V) semicarbazone complexes with the formula cis-VO(2)L, where L=5-bromosalicylaldehyde semicarbazone and 2-hydroxynaphtalen-1-carboxaldehyde semicarbazone have been synthesized and characterized by (1)H and (13)C NMR, Raman and FTIR spectroscopies. Results were compared with those previously reported for other three analogous complexes of this series. The five complexes were tested in three different human tumor cell lines for bioactivity as potential anti-tumor agents, showing selective cytotoxicity on TK-10 cell line. Results showed that structural modifications on the semicarbazone moiety could have a significant effect on the anti-tumor activity of the vanadium complexes. In addition, the electrochemical behavior of all the complexes was studied. No apparent correlation could be demonstrated between reduction potentials of the complexes and their anti-tumor activities. The molecular structure of the novel [V(V)O(2)(5-bromosalicylaldehyde semicarbazone)] complex was solved by X-ray diffraction methods. The vanadium atom shows a distorted square pyramidal coordination sphere. The (VO(2))(+) cation is coordinated to a nearly planar (L)(-) anion acting as a tridentate ligand through both oxygen and one nitrogen atoms.     

Palladium(II) complexes of 2-benzoylpyridine-derived thiosemicarbazones: spectral characterization, structural studies and cytotoxic activity

Palladium(II) complexes of 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N4-methyl (H2Bz4M) and N4-phenyl (H2Bz4Ph) derivatives were obtained and fully characterized. [Pd(2Bz4DH)Cl] (1) crystallizes in the monoclinic space group P21/c with a=11.671(1), b=10.405(1), c=13.124(1), beta=115.60(1) degrees and Z=4; [Pd(2Bz4M)Cl] (2) in the monoclinic space group P21/c with a=9.695(1), b=15.044(1), c=10.718(1) A, beta=105.38(1) degrees and Z=4 and [Pd(2Bz4Ph)Cl] (3) in the triclinic space group P1 with a=9.389(1), b=13.629(1), c=15.218(1) A, alpha=70.25(1), beta=73.46(1), gamma=83.57(1) degrees and two independent molecules per asymmetric unit (Z=4). All complexes show a quite similar planar fourfold environment around palladium(II). A negatively charged organic molecule acts as a tridentate ligand and binds to the metal through the pyridine nitrogen, the imine nitrogen and the sulfur atom. A chloride ion occupies the fourth coordination site. The planar complexes stack nearly parallel to one another in the lattice conforming a layered crystal structure. The cytotoxic activity of the thiosemicarbazones and their metal complexes was tested against the MCF-7, TK-10 and UACC-62 human tumor cell lines. The ligands exhibit lower values of GI50 and LC50 than the complexes, H2Bz4Ph being the most active with GI50<0.003 microM; LC50=13.4 microM; GI50=9.3 microM, LC50=12.9 microM; GI50<0.003, LC50=13.8 microM in the MCF-7, TK-10 and UACC-62 cell lines, respectively. Among the complexes, [Pd(2Bz4Ph)Cl] (3) exhibited the lowest values of GI50 in the three studied cell lines.     

Ecogeographic analysis of morphological and life-history variation in the Italian treefrog

We describe the spatial pattern of variation in body size, body shape, and adult population age structure of the Italian treefrog (Hyla intermedia). By means of a non-parametric test of matrix association (the Partial Mantel Test), we investigate the role of climate and geography in explaining the patterns of phenotypic variation. Body size is the most important source of morphometric variation, both at intra- and inter-populational levels. Body shape, despite its secondary role in explaining variation, still maintains high discriminative power among populations. Age structure differs significantly among populations, since body size correlates positively to age, these differences partly explain geographic variation of body size. The patterns of variation in both age and body size are congruent with climate variation, suggesting causal relationship. However, we find no evidence for adaptive explanations and suggest that climate-induced demographically differential survivorship might be the proximate cause responsible for the associations observed. Unlike body size, body shape varies congruently with the pattern of between-population geographic distances, which we show to be highly correlated with their genetic distances, thus suggesting isolation by distance as the proximate cause of the association.     

Synthesis and biological properties of new 5-nitroindazole derivatives

A series of new 3-alkoxy- or 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5-nitroindazoles have been synthesized and their trichomonacidal, antichagasic and antineoplastic properties studied. Five derivatives (5, 6, 8, 9 and 17) showed remarkable trichomonacidal activity against Trichomonas vaginalis at 10 microg/mL concentration. Three compounds (8, 10, 11) exhibited interesting antichagasic activity and these same compounds moderate antineoplastic activity against TK-10 and HT-29 cell lines. Unspecific cytotoxicity against macrophages has also been evaluated and only compounds 9, 10 and 11 resulted cytotoxic at the higher dose evaluated (100 microg/mL), loosing cytotoxicity at lower doses. QSAR studies have been carried out. X-ray crystallographic study of compound 8 has been performed.     

A WASp-VASP complex regulates actin polymerization at the plasma membrane

Proteins of the Wiskott-Aldrich syndrome and Ena/VASP families both play essential functions in the regulation of actin dynamics at the cell leading edge. However, possibilities of functional interplay between members of these two families have not been addressed. Here we show that, in hemopoietic cells, recruitment of the C-terminal VCA (Verprolin homology, Cofilin homology, Acidic) domain of WASp at the plasma membrane by a ligand technique using rapamycin as an intermediate is not sufficient to elicit efficient Arp2/3 complex-mediated actin polymerization. Other domains of WASp, in particular the proline-rich domain, are required for the formation of actin-rich structures. An in vitro analysis demonstrates that the proline-rich domain of WASp binds VASP with an affinity of approximately 10(6) M(-1). In addition, WASp and VASP both accumulate in actin-rich phagocytic cups. Finally, in a reconstituted motility medium, VASP enhances actin-based propulsion of WASp-coated beads in a fashion reminiscent of its effect on Listeria movement. We propose that VASP and WASp cooperation is essential in stimulating actin assembly and membrane protrusion at the leading edge.     

In silico identification of novel selenoproteins in the Drosophila melanogaster genome

In selenoproteins, incorporation of the amino acid selenocysteine is specified by the UGA codon, usually a stop signal. The alternative decoding of UGA is conferred by an mRNA structure, the SECIS element, located in the 3′-untranslated region of the selenoprotein mRNA. Because of the non-standard use of the UGA codon, current computational gene prediction methods are unable to identify selenoproteins in the sequence of the eukaryotic genomes. Here we describe a method to predict selenoproteins in genomic sequences, which relies on the prediction of SECIS elements in coordination with the prediction of genes in which the strong codon bias characteristic of protein coding regions extends beyond a TGA codon interrupting the open reading frame. We applied the method to the Drosophila melanogaster genome, and predicted four potential selenoprotein genes. One of them belongs to a known family of selenoproteins, and we have tested experimentally two other predictions with positive results. Finally, we have characterized the expression pattern of these two novel selenoprotein genes.     

Seminal vesicle epithelium as a potential pitfall in the cytodiagnosis of presacral masses. A report of two cases

BACKGROUND: Whenever abdominoperineal resection is performed because of a rectal adenocarcinoma, the prostate and seminal vesicles may be displaced backward to the presacral space, giving rise to a false radiologic image of a presacral tumor. Due to cytologic atypia associated with the epithelium of seminal vesicles, there is a real possibility, in fine needle aspiration biopsy (FNAB), of erroneously giving a malignant diagnosis. CASES: Two men, aged 53 and 57 years, presented with presacral masses three months and six years, respectively, after abdominoperineal resection for rectal adenocarcinoma. In both cases, FNAB smears showed some groups and single cells with large and irregular nuclei. These cells suggested a recurrence of carcinoma. The presence of cytoplasmic coarse pigment and a background with spermatozoa and blobs of inspissated secretory product were sufficient to determine that these presacral masses represented the seminal vesicles. CONCLUSION: Awareness that seminal vesicles may give rise to a radiologic impression of presacral tumor after abdominoperineal resection of the rectum will avoid unnecessary FNAB and a cytologic false positive diagnosis of colorectal adenocarcinoma.     

Ovarian and adrenal influence on the ontogenesis of uterine cytosol and nuclear receptors of estrogens

Adrenal and ovarian relative influence over rat uterus estrogenic receptor, both cytosolic (RcE) and nuclear (RnE) ontogenesis, has been studied. Ovarian influence has been studied by practising bilateral ovariectomy the first day of life and examining estrogenic receptor content evolution from, birth to puberty in these ovariectomized animals (OVX1) by comparison with the normal ones. This influence seems to be of scarce importance until the 20th day of life, since estrogenic receptors content is practically coincident in the OVX1 animals and in the control ones. From the 20th day, ovarian secretion influence increases and estrogenic receptor evolution starts evolving in a different way in the two types of animals. Adrenal influence has been studied by practising bilateral adrenalectomy on the 10th or 30th day of life to OVX1 animals or else OVX and ADX on the 10th or 30th day. Adrenal influence in the upkeep of high estrogen receptor levels on the 10th day, seems to be important, since in the absence of these glands it decreases in a considerable way. The situation is different on the 30th day. At this age ovarian secretion seems to be the most important in maintaining estrogen receptor levels, while adrenal secretion effects tend to inhibit them, especially RnE.     

AFM characterization of solid-supported lipid multilayers prepared by spin-coating

Lipids are the principal components of biologically relevant structures as cellular membranes. They have been the subject of many studies due to their biological relevance and their potential applications. Different techniques, such as Langmuir-Blodgett and vesicle-fusion deposition, are available to deposit ordered lipid films on etched surfaces. Recently, a new technique of lipid film deposition has been proposed in which stacks of a small and well-controlled number of bilayers are prepared on a suitable substrate using a spin-coater.We studied the morphological properties of multi-layers made of cationic and neutral lipids (DOTAP and DOPC) and mixtures of them using dynamic mode atomic force microscopy (AFM). After adapting and optimizing, the spin-coating technique to deposit lipids on a chemically etched Silicon (1,0,0) substrate, a morphological nanometer-scale characterization of the aforementioned samples has been provided. The AFM study showed that an initial layer of ordered vesicles is formed and, afterward, depending on details of the spin-coating preparation protocol and to the dimension of the silicon substrate, vesicle fusion and structural rearrangements of the lipid layers may occur.The present data disclose the possibility to control the lipid's structures by acting on spin-coating parameters with promising perspectives for novel applications of lipid films.     

Internal and External Dynamics in Language: Evidence from Verb Regularity in a Historical Corpus of English

Human languages are rule governed, but almost invariably these rules have exceptions in the form of irregularities. Since rules in language are efficient and productive, the persistence of irregularity is an anomaly. How does irregularity linger in the face of internal (endogenous) and external (exogenous) pressures to conform to a rule? Here we address this problem by taking a detailed look at simple past tense verbs in the Corpus of Historical American English. The data show that the language is open, with many new verbs entering. At the same time, existing verbs might tend to regularize or irregularize as a consequence of internal dynamics, but overall, the amount of irregularity sustained by the language stays roughly constant over time. Despite continuous vocabulary growth, and presumably, an attendant increase in expressive power, there is no corresponding growth in irregularity. We analyze the set of irregulars, showing they may adhere to a set of minority rules, allowing for increased stability of irregularity over time. These findings contribute to the debate on how language systems become rule governed, and how and why they sustain exceptions to rules, providing insight into the interplay between the emergence and maintenance of rules and exceptions in language.