A NanoLuc-Based Transactivation Assay in Plants.

Protein-DNA interactions are determinant of the regulation of gene expression in living organisms. Luminescence studies have been used in a wide range of techniques to identify how gene transcription can be regulated by proteins such as transcription factors (TFs). Despite the great advances in the use of luciferases as reporters in the performance of this mechanism, some of them still have disadvantages that have been tried to be solved by the generation of new luciferases that induce a more stable and perfectly visualizable reaction. NanoLuc is a recently described luciferase that has been characterized by its efficient, stable, and powerful luminescence. These qualities have been considered to create a new and efficient reporter system to detect protein-DNA interactions. In this chapter, we take advantage of NanoLuc and describe its use in a reliable procedure to detect protein-DNA interactions in Nicotiana benthamiana extracts and entire leaves.

Caracterización de los pacientes con diagnóstico de cáncer de la glándula tiroides atendidos en Hospital Escuela Dr. Roberto Calderón Gutiérrez, Managua- Nicaragua durante el año 2016 / Characterization of patients diagnosed with thyroid gland cancer treated at Dr. Roberto Calderón Gutiérrez School Hospital, Managua- Nicaragua during 2016

OBJETIVO. Caracterizar a los pacientes con diagnóstico de cáncer de la glándula tiroides atendidos en el Hospital Escuela Roberto Calderón Gutiérrez. Managua, Nicaragua en el año 2016. DISEÑO. Se realizó un estudio de descriptivo, retrospectivo de corte transversal en 65 pacientes con diagnóstico de cáncer de la glándula tiroides obteniendo la información contemplada en los expedientes clínicos. RESULTADOS. De los 65 casos estudiados fueron 47.7% en edades entre los 30 y 50 años, 72.3% del sexo femenino, 41.5% amas de casa como principal ocupación, antecedentes de cáncer de tiroides en el paciente en el 23.1% 92.3% presentaron masa en cuello como manifestación clínica con nódulos con diámetros entre 1 y 4 cm (63.1%), periodo de evolución de la enfermedad de 2 a 5 años, cáncer recurrente en 15 casos, 81.5% de los pacientes con función tiroidea normal, 93.4% clasificación TI-RADS y 92.7% clasificación de sugerente de malignidad o malignos con abordaje quirúrgico en el 100% de los casos y Yodoterapia en el 41.7%. CONCLUSIÓN. El cáncer de tiroides tiene una tendencia ascendente en los últimos años al igual que el resto de cánceres por lo que debe estandarizarse el abordaje diagnóstico para la detección en etapas tempranas

The Year's New Drugs & Biologics - 2009.

This annual article presents new drugs and biologics that were launched or approved for the first time during the previous year. In 2009, 51 new medicines and vaccines reached their first markets. Line extensions (new indications, new formulations and new combinations of previously marketed products) accounted for more than 30% of the new products launched in 2009. In addition to providing an overview of all drugs and biologics launched or approved for the first time ever in the previous year, this article will also review in further depth the first-in-class drugs launched for the first time last year, providing a better understanding of their novel mechanisms of action; an analysis of the discovery and development periods for the year's new products; and a comprehensive overview of drug repositioning as a strategy for extending the life spans of medicines. We also provide a brief glimpse at selected drugs and biologics which could reach their first markets in the foreseeable future.

Overcoming the obstacles in the pharma/biotech industry: 2009 update.

The research-based biopharmaceutical industry faced new challenges during 2009, many rooted in the global economic recession, which further complicated a situation that was already characterized by the obstacles traditionally debated in this and other publications: generic competition, patent expirations and accusations of declining innovation. Once again, companies have been forced to seek out new strategies (mergers, acquisitions, licensing deals, offshore clinical testing and more) in order to cut costs and fill the gaps in their R&D pipelines. However, it is conceivable that the existing R&D model has limitations that can no longer be overcome via these traditional strategies and that the time has come for an entirely new model.

EPR/spin-trapping study of free radical intermediates in the photolysis of trifluoromethyl ketones with initiators.

Photolysis of trifluoromethyl ketones (TFMKs) 1a-1e versus the non-fluorinated ketones 2a-2b in the presence of radical initiators by electron paramagnetic resonance spectroscopy has been studied for the first time. The transient radicals generated after irradiation of the ketones were identified by trapping with 2-methyl-2-nitrosopropane (MNP) and 2,4,6-tri-tert-butylnitrosobenzene (TTBNB) as spin traps. TTBNB is a powerful, particularly useful spin trap in these kinds of processes producing anilino and nitroxyl spin adducts due to the ambivalent reactivity on the N and O atoms. In the presence of t-butylperoxide, short-chain TFMKs, such as 1,1,1-trifluoroacetone (1d) and hexafluoroacetone (1e), give rise to detection of the elusive trifluoromethyl radical. In contrast, long-chain TFMKs did not provide clues to prove formation of the trifluoromethyl radical but instead to radicals derived by abstraction of one alpha-methylene proton to the carbonyl. Although TFMKs are quite stable to photodegradation in the absence of initiator, methyl ketone 2b and phenyl ketone 3 produce radicals resulting from abstraction of a gamma-hydrogen to the carbonyl group.

The year's new drugs & biologics - 2008.

This annual article presents new drugs and biologics that were launched or approved for the first time during the previous year. In 2008, 31 new medicines-this figure includes both drugs and biologics for therapeutic use as well as new diagnostic agents-reached their first markets. Line extensions (new indications, new formulations and new combinations of previously marketed products) accounted for more than one-third of the new medicines launched in 2008. In addition to providing an overview of all drugs and biologics launched or approved for the first time ever in the previous year, this article will also review in further depth the first-in-class drugs launched for the first time last year, providing a better understanding of their novel mechanisms of action; an analysis of the discovery and development periods for the year's new products; and a comprehensive overview of drug repositioning as a strategy for extending the life spans of medicines. We also provide a brief glimpse at selected drugs and biologics which could reach their first markets in the foreseeable future.

Overcoming the obstacles in the pharma/biotech industry: 2008 update.

In the face of patent expirations on blockbuster drugs and declining innovation in the industry, pharma/biotech companies are restructuring their research and development operations and are pursuing an aggressive strategy of acquisitions, licensing deals and research collaborations in an attempt to fill the gaps in their product pipelines.

Aquatic ecotoxicity of a pheromonal antagonist in Daphnia magna and Desmodesmus subspicatus.

Evaluation of the ecotoxicological potential of (Z)-11-hexadecenyl trifluoromethyl ketone (Z11-16:TFMK), a new biorational agent with high prospective features to control the Mediterranean corn borer Sesamia nonagrioides in infested maize fields, in comparison to the parent pheromone compound (Z)-11-hexadecenyl acetate (Z11-16:Ac) is described. Acute and sublethal toxicity tests of both compounds against the cladoceran Daphnia magna and the chlorophyte Desmodesmus subspicatus were conducted, the endpoints being immobilisation and feeding inhibition for Daphnia and growth rate inhibition for Desmodesmus. In addition, effects on B esterases including cholinesterase and carboxylesterase activities in Daphnia were also assessed to evaluate the mode of action of both chemicals. Toxicities of both compounds were moderate with EC(50) values ranging from 3.11 to 103.74mgl(-1) in algae growth, from 0.07 to 1.20mgl(-1) in Daphnia survival, and from 0.10 to 0.53mgl(-1) in Daphnia feeding rate. In all cases Z11-16:TFMK was more toxic than the naturally occurring pheromone component. Serine esterase assays showed a strong inhibition of the carboxylesterase activities in Daphnia at concentrations with apparently no effects on survival or feeding, suggesting that inhibition of other key esterases may be the possible mechanism of toxicity of this compound. The results obtained have been related with some physico-chemical properties of the compounds, such as water solubility and octanol-water partition coefficient, suggesting that Z11-16:TFMK may affect aquatic organisms at lower concentrations than expected from non-polar narcosis.

Arylboronic acids and arylpinacolboronate esters in Suzuki coupling reactions involving indoles. Partner role swapping and heterocycle protection.

Yields of Suzuki couplings involving indoles depended upon (i) whether arylboronic acids or arylpinacolboronate esters were used, (ii) whether the heterocycle was the aryl halide or the arylboron coupling partner, and (iii) whether the heterocycle was protected or not. Highest yields, which were unaffected by incorporating Boc or Tos protection at the heterocyclic nitrogen, were obtained when indole bromides were reacted with phenylboronic acids. When indolylboronic acids were reacted with phenyl bromides, yields were somewhat lower and depended on the nitrogen substituent, being highest in the absence of protection, lower in the presence of the Boc group, and lowest of all with the Tos group. Arylpinacolboronate esters were less reactive than arylboronic acids. They required considerably longer reaction times and furnished generally lower yields of biaryl. Furthermore, irrespective of whether the heterocycle was the aryl bromide or the arylpinacolboronate ester, these yields were highest when it was protected with the Tos group. Yields were lower with the Boc group, and unprotected heterocycles gave only traces of biaryl. Careful selection of arylboron reagent, of coupling partner roles, and of protecting groups are essential to ensuring optimum results in these Suzuki couplings. These results may also be relevant to couplings involving other substrates.