Metabolomic evaluation of Mitomycin C and rapamycin in a personalized treatment of pancreatic cancer

In a personalized treatment designed for a patient with pancreatic cancer resistant to other treatments, the success of Mitomycin C (MMC) has been highlighted. This was revealed in a murine xenograft tumor model encompassing pancreatic adenocarcinoma cells extracted from the patient. The patient was found to exhibit a biallelic inactivation of the PALB2 gene, involved in DNA repair in addition to another mutation in the TSC2 gene that induces susceptibility of the tumor to therapeutic targets of the PI3K-mTOR pathway. The aim of the study was to apply metabolomics to elucidate the modes of action of each therapy, suggesting why MMC was so successful in this patient and why it could be a more popular choice in future pancreatic cancer treatment. The effectiveness of MMC compared to rapamycin (RM), another relevant therapeutic agent has been evaluated through liquid- and gas-chromatography mass spectrometry-based metabolomic analyses of the xenograft tumors. The relative concentrations of many metabolites in the xenograft tumors were found to be increased by MMC relative to other treatments (RM and a combination of both), including a number that are involved in central carbon metabolism (CCM). Metabolic fingerprinting revealed statistically significantly altered pathways including, but not restricted to, the pentose phosphate pathway, glycolysis, TCA cycle, purine metabolism, fatty acid biosynthesis, in addition to many significant lipid and amino acid alterations. Given the genetic background of the patient, it was expected that the combined therapy would be most effective; however, the most effective was MMC alone. It is proposed that the effectiveness of MMC is owed to its direct effect on CCM, a vital region of tumor metabolism

Improved prediction of the optical properties in pi-conjugated polymers: the case of benzochalcogenodiazole-based copolymers with different heteroatom substitution

Donor−acceptor (D−A) approach to conjugated polymer design has become a widely used method for preparing conjugated polymers with narrow band gaps.1 One outstanding D−A polymer is poly(cyclopentadithiophene)benzothiadiazole, PCPDTBT (P1 in Figure 1), for which power conversion efficiencies in solar cells of 4.5-5.5% are reported.2 In this work, we use resonance Raman (RR) and density functional theory (DFT) calculations to investigate the tuning of the electronic and structural properties of cyclopentadithiophene-benzochalcogenodiazole D−A polymers, wherein a single atom in the benzochalcogenodiazole unit is varied from sulfur to selenium to tellurium (Fig. 1).3 Sophisticated DFT calculations have been carried out using long-range corrected functionals, considering both tuned and default range-separation parameters, aiming at predicting their optical and charge transport properties. In addition, the nature of the electronic excitation is described by analyzing the enhancement pattern in the RR spectra using Raman excitation wavelengths coincident with the various transitions in the copolymers.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Modelling the optical properties of Benzochalcogenodiazole-based Copolymers using Tuned Range-Separated Hybrid Functionals

Since the discovery of organic semiconductors, these systems have been deeply investigated and many strategies to module their optical and electronic properties have been established. In this sense, Donor-acceptor (D−A) approach to conjugated polymer design has become a widely used method for preparing conjugated polymers with narrow band gaps. This approach involves synthesizing a polymer with a delocalized π-electron system that comprises alternating electron-rich (donor) and electron-deficient (acceptor) repeat units. The combination of high-lying HOMO levels (residing on the donor units) and low-lying LUMO levels (residing on the acceptor units) results in an overall narrow band gap for the polymer. In this sense, poly(cyclopentadithiophene)benzothiadiazole is a D−A polymer for which power conversion efficiencies in solar cells of 5 6 % are reported. In this work, we use density functional theory (DFT) calculations to investigate the tuning of the electronic and structural properties of cyclopentadithiophene ben zochalcogenodiazole D−A polymers, wherein a single atom in the benzochalcogenodiazole unit is varied from sulfur to selenium to tellurium. Resonance Raman (RR) spectroscopy is also used to describe the nature of the electronic excitations. Improved prediction of the optical properties h as been obtained by using long range corrected functionals functionals, considering both tuned and default range separation parameters, aiming at predicting their optical and charge transport properties.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Spectroelectrochemical Raman Study of a Novel Well-Barrier-Well Vinylene-Bridged-Octithiophene Oligomer: An Analysis of the Conjugation Length and of the Electronic Defects Created upon Doping

We have studied the Fourier transform Raman (FT-Raman) spectra of a novel well-barrier-well vinylenebridged-octithiophene in neutral and doped states. The compound was doped in a reaction with iodine vapors and electrochemically in the form of a thin film coated platinum electrode. We have analyzed the evolution of the Raman spectral pattern upon oxidation of the material at different anodic potentials. The data indicate that the oxidation process takes place in two well-differentiate steps: the initial formation of the radical cation followed by the generation of the dication. The comparison of the spectroscopic data with those previously obtained on a related vinylene-bridged-quaterthiophene enabled us to draw conclusions about the effective π-conjugation length in neutral state. RHF/3-21G* theoretical calculations have been performed to analyze the changes of the geometrical parameters when going from the neutral to the doped forms

Amplified Spontaneous Emission in Pentathienoacene Dioxides by Direct Optical Pump and by Energy Transfer: Correlation with Photophysical Parameters

Amplified spontaneous emission (ASE) is observed, under optical pump, in polystyrene films doped with two pentathienoacene derivatives functionalised with thienyl-S,S-dioxide groups (compounds 2 and 3). The effect of the dioxide groups on the ASE properties is analysed by comparing the performance with that of its corresponding non-oxidized analogue (1). Films containing either 2 or 3 show ASE at 511 and 574 nm, respectively, when excited directly (at 435 nm) on their absorption bands, showing thresholds and linewidths larger than those obtained from films doped with 1, pumped at 355 nm. ASE is also observed under excitation at 355 nm, in samples containing 1 (host) and either 2 or 3 (guests), due to energy transfer from host to guest. For the blends with 3, the ASE threshold is lower than that obtained when the films are excited directly. Results are interpreted in terms of the photophysical parameters such as absorption capacity, fluorescence efficiency, singlet-to-triplet intersystem crossing leading to triplet-triplet re-absorptions, bimolecular energy-transfer efficiency, efficiency of internal conversion process, etc. State-of-the-art quantum chemical calculations are used in the interpretation of the experimental results.Authors from the University of Alicante acknowledge support from the Spanish Government (MINECO) and the European Community (FEDER) through grants MAT2008–06648-C02–01 and MAT2011–28167-C02–01. The work at the University of Málaga is supported by the MEC projects CTQ2012–33733 and by the PO9–4708 project by the Junta de Andalucía. Raquel Rondão acknowledges FCT for a PhD grant (SFRH/BD/38882/2007). D.A.S.F. gratefully acknowledges the financial support from the Brazilian Research Councils: CAPES, CNPq (grant 303084/2010–3) and FAP-DF (Fundação de Apoio à Pesquisa do Distrito Federal)

Precision Betacarotene Supplementation Enhanced Ovarian Function and the LH Release Pattern in Yearling Crossbred Anestrous Goats

The possible out-of-season effect of beta-carotene supplementation on ovulation rate (OR), antral follicles (AFN), and total ovarian activity (TOA = OR + AFN) as related to the LH release pattern in yearling anestrous goats was evaluated. In late April, Alpine-Saanen-Nubian x Criollo goats (n = 22, 26 N) were randomly allotted to: (1) Beta-carotene (BETA; n = 10, orally supplemented with 50 mg/goat/d; 36.4 ± 1.07 kg live weight (LW), 3.5 ± 0.20 units, body condition score (BCS) or (2) Non-supplemented (CONT; n = 12, 35.2 ± 1.07 kg LW, 3.4 ± 0.2 units BCS). Upon estrus synchronization, an intensive blood sampling (6 h × 15 min) was accomplished in May for LH quantifications; response variables included (pulsatility-PULSE, time to first pulse-TTFP, amplitude-AMPL, nadir-NAD and area under the curve-AUC). Thereafter, an ultrasonography scanning was completed to assess OR and AFN. The Munro algorithm was used to quantify LH pulsatility; if significant effects of time, treatment or interaction were identified, data were compared across time. Neither LW nor BCS (p > 0.05) or even the LH (p > 0.05); PULSE (4.1 ± 0.9 pulses/6 h), NAD (0.47 ± 0.13 ng) and AUC (51.7 ± 18.6 units) differed between treatments. Nonetheless, OR (1.57 vs. 0.87 ± 0.18 units) and TOA (3.44 vs. 1.87 ± 0.45 units) escorted by a reduced TTFP (33 vs. 126 ± 31.9 min) and an increased AMPL (0.55 vs. 0.24 ± 0.9 ng), favored to the BETA supplemented group (p < 0.05), possibly through a GnRH-LH enhanced pathway and(or) a direct effect at ovarian level. Results are relevant to speed-up the out-of-season reproductive outcomes in goats while may embrace translational applications

Comparative study on the clinical-nutritional status of obese postmenopausal women on a weight loss programme based on prepared dishes

Comparative Study; English Abstract; Journal Article;INTRODUCTION Few studies have evaluated the efficacy and reliability of weight loss-focussed prepared food dishes in obese post-menopausal women. OBJECTIVE To compare the efficacy of a weight loss programme based on a balanced hypocaloric diet using prepared dishes* with that of a similar programme based on standard commercially available foods and with a non-intervened control group. A further aim was to evaluate the subjectivity of participants in the preparation of the diet-adjusted dishes based on usually consumed products. SUBJECTS Obese post-menopausal women aged between 55 and 65 years. DESIGN Controlled longitudinal interventional study. METHOD The sample of 75 female volunteers were divided into three groups of 25 women: a control group, who continued to consume their usual non-dietary adjusted meals (CG), an intervened group, treated with a diet adjusted to their individual requirements and based on standard commercially available food (SG), and another intervened group, treated with a similarly adjusted diet but based on prepared dishes (PG). Data were gathered on anthropometric variables, consumption habits and physical activity levels, and clinical-nutritional controls were conducted at the start and every two weeks to the end of the 8-week study in order to evaluate biochemical changes. RESULTS The weight loss was slightly higher in the prepared-dishes group (PG) than in the standard food diet group (SG), but the difference was not statistically significant, whereas it was considerably higher in both groups than in the non-dietary adjusted control group (CG) and this difference was highly significant (losses of 7.60 kg in PG and 7.01 kg in SG versus 2.10 kg in CG (p < 0.01). However, the PG showed a significantly higher (p < 0.01) loss of fatty mass and abdominal circumference versus the SG women. CONCLUSION More weight was lost by the two groups treated with a diet based on prepared dishes or usual food items in comparison to untreated controls, but the diet based on prepared dishes obtained more reliable and higher quality outcomes, achieving a positive change at fatty compartment level and in the abdominal circumference.El presente proyecto ha sido financiado por la empresa Deliline® S. A.YesIntroducción: Son escasos los estudios que hayan evaluado la eficacia y la fiabilidad de los platos de comidas preparadas* enfocadas a la pérdida de peso en la mujer posmenopáusica obesa. Objetivo: Evaluar la eficiencia de un programa de pérdida de peso basado en una ingesta hipocalórica equilibrada, a partir de platos preparados* comparando con otra basada en alimentos de consumo habitual en el mercado y con un grupo control no intervenido. En el presente estudio se pretende, además, valorar la subjetividad de la participante a la hora de preparar los platos ajustados a la dieta de restricción basada en productos de consumo habitual. Sujetos de estudio: mujeres posmenopáusicas obesas, con edad comprendida entre 55-65 años. Diseño del estudio: Estudio longitudinal de intervención y controlado. Metodología: La muestra de 75 mujeres voluntarias se divide en tres grupos de 25 mujeres; uno con alimentación habitual, sin dieta ajustada (GC), otro intervenido mediante tratamiento con una dieta ajustada a los requerimientos individuales, pero con productos de consumo habitual en mercado (GE) y un tercero intervenido con dieta ajustada del mismo modo al anterior, pero con platos preparados (GD). Se registraron datos antropométricos, hábitos de consumo y nivel de actividad física. También se realizaron controles clínico-nutricionales para evaluar cambios bioquímicos al inicio del estudio, cada 2 semanas y al final del estudio, durante 8 semanas. Resultados: El grupo basado en platos preparados GD muestra resultados de pérdida de peso ligeramente mayores, aunque no estadísticamente significativos, al grupo de dieta estándar GE, mostrando, sin embargo, ambos, descensos muy significativos respecto al grupo no ajustado GC (con una pérdida de 7,60 kg en GD, 7,01 kg en el grupo GE y 2,10 kg en GC). Sin embargo, éste grupo de mujeres alimentadas con dieta hipocalórica basada en platos preparados GD, presenta (p < 0,01) una mayor pérdida significativa, tanto de masa grasa como de perímetro abdominal. Conclusión: Las mujeres tratadas con dieta basada en platos preparados GD y las tratadas con dieta ajustada habitual GE presentan una mayor pérdida de peso, pero el grupo GD mostró unos resultados más fiables y de calidad, dado el cambio positivo encontrado a nivel de compartimento graso y en el perímetro abdominal de las participantes del grupo objeto del estudio

Combined Raman spectroscopic and Rietveld analyses as a useful and nondestructive approach to studying flint raw materials at prehistoric archaeological sites

Artículo sobre análisis de espectroscopía

Dengue Fever Seroprevalence and Risk Factors, Texas–Mexico Border, 2004

High seroprevalence of dengue was found on both sides of the border

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.&lt;p&gt;&lt;/p&gt; Methods: Sixty-six non-HLA SNPs showing a P value &#60;10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.&lt;p&gt;&lt;/p&gt; Conclusion: Our results suggest a role of PPARG gene in the development of SSc