Novel bis(thiosemicarbazones) of the 3,5-diacetyl-1,2,4-triazol series and their platinum(ii) complexes: chemistry, antiproliferative activity and preliminary nephrotoxicity studies

Dalton Transactions 40.21 (2011): 5738-5745. Reproduced by permission of The Royal Society of ChemistryThe preparation and characterization of three novel 4N- monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series and their dinuclear platinum complexes are described. The crystal and molecular structure of the [Pt(μ-H3L3)]2 complex derived of 3,5-diacetyl-1,2,4-triazol bis(4N-p- tolylthiosemicarbazone), H5L3, has been resolved by single crystal X-ray diffraction. The ligands coordinate, in an asymmetric dideprotonate form, to the platinum ions in a tridentate fashion (NNS) and S-bridging bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumour properties since are capable of not only circumventing cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in human non-small cell lung cancer NCI-H460 cells. The interactions of these compounds with calf thymus DNA was investigated by UV-vis absorption and a nephrotoxic study, in LLC-PK1 cells, has also been carried outWe are grateful to Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (PI080525), Universidad Autónoma de Madrid and Comunidad de Madrid (CCG08-UAM/SAL-4000) of Spain for financial suppor

3,5-Diacetyl-1,2,4-triazol bis( 4N-substituted thiosemicarbazone) palladium(II) complexes: Synthesis, structure, antiproliferative activity and low toxicity on normal kidney cells

this is the author’s version of a work that was accepted for publication in Journal of Inorganic Biochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Inorganic Biochemistry 105.12 (2011): 1613-1622 DOI http://dx.doi.org/10.1016/j.jinorgbio.2011.08.014Treatment of 4N-monosubstituted bis(thiosemicarbazone) ligands of 3,5-diacetyl-1,2,4-triazol series with lithium tetrachloridopalladate gave the dinuclear complexes of general formula [Pd(μ-H 3L 1-5)] 2, but using dichloridobistriphenylphosphinepalladium(II) salt, the first mononuclear bis(thiosemicarbazone)-palladium-triphenylphosphine complexes of the 3,5-diacetyl-1,2,4-triazol series, [Pd(H 3L 1-5)PPh 3], have been obtained. All the compounds have been characterized by elemental analysis and by IR and NMR spectroscopy, and the crystal and molecular structures of dinuclear complexes [Pd(μ-H 3L 3)] 2 and [Pd(μ-H 3L 5)] 2 as well as mononuclear complexes [Pd(H 3L 1)PPh 3], [Pd(H 3L 2)PPh 3], [Pd(H 3L 3)PPh 3] and [Pd(H 3L 4)PPh 3] have been determined by X-ray crystallography. The new compounds synthesized have been evaluated for antiproliferative activity in vitro against NCI-H460, A2780 and A2780cisR human cancer cell lines. Subsequent toxicity study, on normal renal LLC-PK1 cells, shows that all compounds investigated exhibit very low toxicity on kidney cells with respect to cisplatinWe are grateful to Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (PI080525), Universidad Autónoma de Madrid and Comunidad de Madrid (CCG08-UAM/SAL-4000) of Spain for financial suppor

New bioactive 2,6-diacetylpyridine bis(p-chlorophenylthiosemicarbazone) ligand and its Pd(II) and Pt(II) complexes: Synthesis, characterization, cytotoxic activity and DNA binding ability

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Inorganic Biochemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Inorganic Biochemistry 138 (2014): 16-23 DOI http://dx.doi.org/10.1016/j.jinorgbio.2014.04.017Preparation and characterization of 2,6-diacetylpyridine bis(4N-p-chlorophenylthiosemicarbazone) ligand, H2L, and its palladium(II) and platinum(II) complexes [PdL] and [PtL], is described. The molecular structure of the two new complexes has been determined by single crystal X-ray diffraction. The ligand acts as dianionic tetradentate donor coordinating to the metal center in a square planar geometry through the pyridine nitrogen atom and the azomethine nitrogen and thione sulfur atoms from one thiosemicarbazone arm, the fourth coordination position is occupied by the hydrazine nitrogen atom of the other arm. New free ligand and its metal complexes have been evaluated for antiproliferative activity in vitro against NCI-H460, T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H2L and [PtL] since they are capable of not only circumvent cisplatin resistance in A2780cisR cells but also exhibit high antiproliferative activity in breast cancer T-47D cells. The interaction of H2L with calf thymus DNA was also investigated and its binding constant (Kb) determinedWe are grateful to Ministerio de Economía y Competitividad, Instituto de Salud Carlos III of Spain (PI1100659) for financial suppor

Demo 40. Termómetro de Galileo

Objetivo: Comprobación del Principio de Arquímedes y de la variación de la densidad de un líquido con la temperatura

Exogenous Carbon Compounds Modulate Tomato Root Development

NO3 − is not only a nutrient, but also a signaling compound that plays an important role in several plant processes, like root development. The present study aimed to investigate the effect of three different exogenous C compounds (sucrose, glucose, 2-oxoglutarate) added to NO3 − nutrition on C/N, auxin and antioxidant metabolisms in 10-day-old tomato seedlings. Sucrose and glucose supplementation enhanced primary root (PR) length, lateral root number and root density, while 2-oxoglutarate negatively affected them. This phenomenon was accompanied by a slight increase in NRT2.1 and GS1 gene expression, together with an increase in LAX2 and LAX3 and a decrease in LAX4 in the roots growing under sucrose and glucose sources. The addition of 2-oxoglutarate enhanced the expression of NiR, GDH, PEPC1, LAX1, LAX3 and the antioxidant gene SOD Cl. Taken together, these findings contribute to a better understanding of how these C sources can modulate N uptake and C/N, auxin and antioxidant gene expression, which could be useful for improving nitrogen use efficienc

An LRP6 mutation (Arg360His) associated with low bone mineral density but not cardiovascular events in a caucasian family

We present a family with a rare mutation of the LRP6 gene and for the first time provide evidence for its association with low bone mineral density. Introduction: The Wnt pathway plays a critical role in bone homeostasis. Pathogenic variants of the Wnt co-receptor LRP6 have been associated with abnormal skeletal phenotypes or increased risk of cardiovascular events. Patient and methods: Here we report an index premenopausal patient and her family carrying a rare missense LRP6 pathogenic variant (rs141212743; 0.0002 frequency among Europeans). This variant has been previously associated with metabolic syndrome and atherosclerosis, in the presence of normal bone mineral density. However, the LRP6 variant was associated with low bone mineral density in this family, without evidence for association with serum lipid levels or cardiovascular events. Conclusion: Thus, this novel association shows that LRP6 pathogenic variants may be involved in some cases of early-onset osteoporosis, but the predominant effect, either skeletal or cardiovascular, may vary depending on the genetic background or other acquired factors.Funding: Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Natur

Effect of Fattening Period Length on Intramuscular and Subcutaneous Fatty Acid Profiles in Iberian Pigs Finished in the Montanera Sustainable System

Twenty-four extensively reared Iberian pigs were used to study the influence of fattening period length (30, 60 or 90 days) on the fatty acid profiles of intramuscular and subcutaneous fat and the relationships between both profiles. Regarding fatty acid (FA) percentage, PUFA was greater in backfat and MUFA was greater in intramuscular fat (IMF), regardless of fattening period length. The longer fattening period increased MUFA content in backfat (which had a more marked change in oleic acid) and decreased PUFA content in backfat and IMF, but it did not affect SFA content. Within the three-layer subcutaneous backfat, SFA content was greater in the inner layer, MUFA was greater in the outer layer and PUFA was greater in both of these layers. The few differences in FA composition between both adipose tissues suggest that the changes due to the feeding regime are slow and, therefore, although the length of the fattening phase was increased, the fatty acid profile did not change substantially. The strong relationship between the FA profiles of IMF and backfat might be used to predict one profile from the other one when the latter is more readily available for sampling or analytical reasons

Desarrollo del lenguaje como facilitador social en tres niños con discapacidad auditiva de la ciudad de Ibagué

Entrevistas, formatos de consentimientos, preguntas generadorasEl objetivo de este proyecto de investigación es analizar el desarrollo del lenguaje como facilitador social en 3 niños con discapacidad auditiva de la ciudad de Ibagué, pertenecientes a la institución educativa Niño Jesús de Praga (ITSOR); se observó a los niños en sus tres contextos primordiales familiar, escolar y pares, que permiten evaluar su contexto social y este a su vez, logra el desarrollo de lenguaje como lo propone Bruner, J (1969) quien ha desarrollado una teoría constructivista del aprendizaje, en la que, entre otras cosas, ha descrito el proceso de aprender, los distintos modos de representación y las características de una teoría de la instrucción; la teoría de la instrucción se ocupa de la forma en que lo que uno desea enseñar pueda ser mejor aprendido, de mejorar más que describir el aprendizaje. Esta investigación es de tipo cualitativo y a través de las historias de vida se llegó a la conclusión que el Sistemas de Apoyo a la Adquisición del Lenguaje (LASS) es importante para la adquisición del lenguaje, en cuanto los procesos de representación (Enactivo, Icónico, y Simbólico) se dan sin oralidad porque el lenguaje es un acto comunicativo.The objective of this research project is to analyze the development of language as social facilitator in 3 children with hearing impairment in the city of Ibague, belonging to the school Infant Jesus of Prague (ITSOR) children was observed in three contexts primary family, school and peers, which to assess its social context and this in turn, manages the development of language as proposed by Bruner, J (1969) who has developed a constructivist theory of learning, in which, among other things, described the process of learning, the different modes of representation and the characteristics of a theory of instruction, instructional theory deals with the way I want to teach you to be better learned, to improve rather than describing the learning. This research is qualitative and through the life stories is concluded that the Support System Language Acquisition (LASS) is important for language acquisition, as the processes of representation (enactive, iconic, and symbolic) are given without orality because language is a communicative act

The regulated expression of chimeric tyrosine hydroxylase–insulin transcripts during early development

Biological complexity does not appear to be simply correlated with gene number but rather other mechanisms contribute to the morphological and functional diversity across phyla. Such mechanisms regulate different transcriptional, translational and post-translational processes and include the recently identified transcription induced chimerism (TIC). We have found two novel chimeric transcripts in the chick and quail that result from the fusion of tyrosine hydroxylase (TH) and insulin into a single mature transcript. The th and insulin genes are located in tandem and they are generally transcribed independently. However, it appears that two chimeric transcripts containing exons from both the genes can also be produced in a regulated manner. The TH–INS1 and TH–INS2 chimeras differ in their insulin gene content, and they encode two novel isoforms of the TH protein with markedly reduced functionality when compared with the canonical TH. In addition, the TH–INS1 chimeric mRNA generates a small amount of insulin. We propose that TIC is an additional mechanism that can be employed to further regulate TH and insulin expression according to the specific needs of developing vertebrates

Putrescine biosynthetic pathways modulate root growth differently in tomato seedlings grown under different N sources

The biosynthesis of putrescine is mainly driven by arginine decarboxylase (ADC) and ornithine decarboxylase (ODC). Hence, in this study, we generated independent ADC and ODC transgenic silenced tomato lines (SilADC and SilODC, respectively) to test the effect of defective ADC and ODC gene expression on root development under nitrate (NN) or ammonium (NA) conditions. The results showed that SilODC seedlings displayed an increase in ADC expression that led to polyamine accumulation, suggesting a compensatory effect of ADC. However, this effect was not observed in SilADC seedlings. These pathways are involved in different growth processes. The SilADC seedlings showed an increase in fresh weight, shoot length, lateral root number and shoot:root ratio under the NN source and an enhancement in fresh weight, and shoot and root length under NA conditions. However, SilODC seedlings displayed greater weight and shoot length under the NN source, whereas a decrease in lateral root density was found under NA conditions. Moreover, two overexpressed ODC lines were generated to check the relevance of the compensatory effect of the ADC pathway when ODC was silenced. These overexpressed lines showed not only an enhancement of almost all the studied growth parameters under both N sources but also an amelioration of ammonium syndrome under NA conditions. Together, these results reflect the importance of both pathways in plant growth, particularly ODC silencing, which requires compensation by ADC induction.Funding for open access charge: CRUE-Universitat Jaume