An Investigation of the Role of Macular Pigment in Attenuating Photostress through Comparison between Blue and Green Photostress Recovery Times

Purpose: Photostress recovery time (PSRT) is the time required for the macula to return to its normal functioning after the bleaching of cone photopigments due to light exposure, usually white. This work investigates the role of macular pigment (MP) as an optical filter that attenuates photostress by analyses of PSRT at different wavelengths. Methods: Thirty-nine subjects (19–28 years) were exposed to blue/green photostress varying in irradiance. During photostress, pupil constriction (Cp) was measured. Twenty-seven subjects (20–27 years) were exposed to white photostress. After 25 s of photostress, the time (PSRT) required to read correctly a 0.2 logMAR letter was measured. Correlation was studied between PSRT, CP, and irradiance. Statistical significance of differences between PSRTs was evaluated at Log(irradiance(quanta s−1 cm−2)) = 14 by Student’s t statistics. Results: Cp and PSRT were found linearly correlated to Log(irradiance) for blue, green, and white. At Log(irradiance(quanta s−1 cm−2)) = 14, blue and green mean PSRTs resulted different (p 0.05). Conclusions: MP plays the role of an optical filter attenuating photostress. PSRT was substantially proportional to the number of incident photons corrected for the MP optical absorption, regardless of their wavelength

Sensitivity of simulated soil water content, evapotranspiration, gross primary production and biomass to climate change factors in Euro-Mediterranean grasslands

Grassland models often yield more uncertain outputs than arable crop models due to more complex interactions and the largely undocumented sensitivity of grassland models to environmental factors. The aim of the present study was to assess the impact of single-factor changes in temperature, precipitation, and atmospheric [CO2] on simulated soil water content (SWC), actual evapotranspiration (ET), gross primary production (GPP) and yield biomass, and also to link the sensitivity analysis with experimental results. We employed an unprecedented multi-model framework consisting of seven grassland models at nine sites with different environmental characteristics in Europe and Israel, with two management options at three sites. For warming/cooling and wetting/drying, models showed general consistency in the direction of SWC and ET changes, but less agreement regarding GPP and biomass changes. The simulated responses consistently revealed an overall positive effect of CO2 enrichment on GPP and biomass, while the direction of change differed for SWC and ET. Comparing with single-factor experimental manipulations, SWC simulations slightly underestimated the observed effect of warming, while the overall mean model sensitivity for biomass (+7.5%) closely matched the mean response observed with 1–2 °C warming (+6.6%). The models exhibited lower sensitivity of SWC to wetting or drying compared to the experiments. The overall mean sensitivity of biomass to drying was -4.3%, contrasting with the mean experimental effect size of -9.6%, which proved to be more realistic than the mean wetting effect (+3.2%, against +38.9% in the field trials). The simulated sensitivity of SWC to CO2 enrichment was markedly underestimated, while the biomass response (+12.0%) closely matched the observations (+17.5%). Although the multi-model averaging did not manifestly improve the realism of the simulations, it ensured a realistic response in the direction of change to varying conditions. The results suggest a paradigm shift in grassland modelling meaning that the usual practice of model optimisation/validation needs to be complemented by a sensitivity analysis following the approach presented. The results also highlight the importance of model improvements, especially in terms of soil hydrology representation, a key environmental driver of grassland functioning

Biomarkers of sensitivity to potent and selective antitumor 2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F203) in ovarian cancer

2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F203, NSC 703786) lysylamide belongs to a novel mechanistic class of antitumor agents. It elicits activity against ovarian, breast, kidney and colorectal cancer models. In sensitive breast cancer cells, 5F203 activates aryl hydrocarbon receptor (AhR) signaling. Herein, we evaluate the role of AhR in 5F203 activity in two ovarian cancer cell lines: IGROV-1 (sensitive to 5F203), SKOV-3 (resistant to this agent). In addition, cancer cells have been isolated from ascites fluid of ovarian cancer patients; sensitivity to 5F203 and concurrent AhR signal transduction has been examined in ascites-isolated ovarian cancer patients' cells. 5F203 induced enhanced CYP1A1 expression, AhR translocation and ROS formation in IGROV-1 cells and ascites-isolated ovarian cancer cells that were sensitive to 5F203. In IGROV-1 cells 5F203-induced ROS formation was accompanied by JNK, ERK and P38MAPK phosphorylation, DNA damage and cell cycle arrest prior to apoptosis. In contrast, 5F203 failed to induce CYP1A1 expression, AhR translocation or oxidative stress in 5F203-resistant SKOV-3 cells, or in ovarian cancer ascites cells inherently resistant to this agent. We propose that AhR may represent a new molecular target in the treatment of ovarian tumors and 5F203 may exemplify a potential novel treatment. Furthermore, putative biomarkers of sensitivity to this agent have been identified.Fil: Callero, Mariana Alejandra. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Luzzani, Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Dios, Diana O.. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Bradshaw, Tracey D.. The University Of Nottingham; Reino UnidoFil: Loaiza Perez, Andrea Irene. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

One-pot synthesis of nano-crystalline MCM-22

[EN] Nano-crystalline MCM-22 zeolite was synthesized in a one-pot procedure by the use of an organosilane (dimethyl-octadecyl-(3-trimethoxysilylpropyl)-ammonium chloride, TPOAC) in the zeolite synthesis gel. This crystal growth inhibition procedure introduced mesopores in the MCM-22 crystallites. The lower mechanical stability of the nano-crystalline MCM-22 zeolite compared with bulk MCM-22 can be countered to some extent by pillaring. The increased external surface of the microporous zeolite domains resulted in increased accessibility of the Bronsted acid sites, as followed from the better performance in liquid-phase benzene alkylation with propylene as compared with bulk MCM-22. The increased accessibility of the internal acid sites in Mo-loaded hierarchical MCM-22 was also evident from the improved benzene selectivity during methane aromatization. Silylation of hierarchical Mo/MCM-22 was detrimental for the catalytic performance in MDA. The nano-crystalline MCM-22 has physico-chemical and catalytic properties intermediate between those of MCM-22 and ITQ-2 with the benefit over ITQ-2 that it can be synthesized in a single step. (C) 2015 Elsevier Inc. All rights reserved.Funding from the 7th Framework Program of the European Commission through the Collaborative Project Next-GTL (agreement no 229183) and financial support by the Spanish Government-MINECO through "Severo Ochoa" (SEV 2012-0267), Consolider Ingenio 2010-Multicat (CSD2009-00050) and MAT2012-31657 are acknowledged. Marta E. Martinez Armero thanks MINECO for economical support through pre-doctoral fellowship for doctors training (BES-2013-066800). The authors thank B. Esparcia for technical assistance.Tempelman, CHL.; Portilla Ovejero, MT.; Martínez Armero, ME.; Mezari, B.; De Caluwe, NGR.; Martínez, C.; Hensen, EJM. (2016). One-pot synthesis of nano-crystalline MCM-22. Microporous and Mesoporous Materials. 220:28-38. https://doi.org/10.1016/j.micromeso.2015.08.018S283822

Effects of Weight Loss in Metabolically Healthy Obese Subjects after Laparoscopic Adjustable Gastric Banding and Hypocaloric Diet

Weight loss in metabolically healthy obese (MHO) subjects may result in deterioration of cardio-metabolic risk profile. We analyzed the effects of weight loss induced by laparoscopic adjustable gastric banding (LAGB) on cardio-metabolic risk factors in MHO and insulin resistant obese (IRO) individuals. This study included 190 morbidly obese non-diabetic subjects. Obese individuals were stratified on the basis of their insulin sensitivity index (ISI), estimated from an OGTT, into MHO (ISI index in the upper quartile) and IRO (ISI in the three lower quartiles). Anthropometric and cardio-metabolic variables were measured at baseline and 6-months after LAGB. Six months after LAGB, anthropometric measures were significantly reduced in both MHO and IRO. Percent changes in body weight, BMI, and waist circumference did not differ between the two groups. Fasting glucose and insulin levels, triglycerides, AST, and ALT were significantly reduced, and HDL cholesterol significantly increased, in both MHO and IRO subjects with no differences in percent changes from baseline. Insulin sensitivity increased in both MHO and IRO group. Insulin secretion was significantly reduced in the IRO group only. However, the disposition index significantly increased in both MHO and IRO individuals with no differences in percent changes from baseline between the two groups. The change in insulin sensitivity correlated with the change in BMI (r = −0.43; P<0.0001). In conclusion, our findings reinforce the recommendation that weight loss in response to LAGB intervention should be considered an appropriate treatment option for morbidly obese individuals regardless of their metabolic status, i.e. MHO vs. IRO subjects

Synergistic Antitumor Effects of Novel HDAC Inhibitors and Paclitaxel In Vitro and In Vivo

Preclinical studies support the therapeutic potential of histone deacetylases inhibitors (HDACi) in combination with taxanes. The efficacy of combination has been mainly ascribed to a cooperative effect on microtubule stabilization following tubulin acetylation. In the present study we investigated the effect of paclitaxel in combination with two novel HDACi, ST2782 or ST3595, able to induce p53 and tubulin hyperacetylation. A synergistic effect of the paclitaxel/ST2782 (or ST3595) combination was found in wild-type p53 ovarian carcinoma cells, but not in a p53 mutant subline, in spite of a marked tubulin acetylation. Such a synergistic interaction was confirmed in additional human solid tumor cell lines harboring wild-type p53 but not in those expressing mutant or null p53. In addition, a synergistic cytotoxic effect was found when ST2782 was combined with the depolymerising agent vinorelbine. In contrast to SAHA, which was substantially less effective in sensitizing cells to paclitaxel-induced apoptosis, ST2782 prevented up-regulation of p21WAF1/Cip1 by paclitaxel, which has a protective role in response to taxanes, and caused p53 down-regulation, acetylation and mitochondrial localization of acetylated p53. The synergistic antitumor effects of the paclitaxel/ST3595 combination were confirmed in two tumor xenograft models. Our results support the relevance of p53 modulation as a major determinant of the synergistic interaction observed between paclitaxel and novel HDACi and emphasize the therapeutic interest of this combination

p53 as a potential predictive factor of response to chemotherapy: feasibility of p53 assessment using a functional test in yeast from trucut biopsies in breast cancer patients

Assessment of the predictive value of p53 requires the testing of large numbers of samples from patients enrolled in prospective phase III clinical trials. The goal of this study was to determine whether p53 status can be determined by p53 yeast functional assay using the limiting amounts of material that can typically be obtained in prospective phase III trials (particularly when chemotherapy is given before surgery). All patients presenting with a clinically palpable tumour which could be considered large enough to perform a trucut biopsy (⩾2 cm breast tumour) were eligible for this study. Two trucut biopsies and one incisional biopsy were performed on the surgical specimens (mastectomy or tumourectomy). Samples were snap frozen and cryostat sections were taken for histology and p53 testing. Thirty patients were included. Three samples out of 90 failed to give any p53 PCR products, probably because these samples contained almost entirely fibrous tissue. Of the 87 samples that could be tested, the incisional and trucut biopsies results were fully concordant in every case. p53 could be defined in 97% of patients by double trucut biopsy. Eight out of 30 tumours tested were mutant for p53 (27%). p53 status can be reliably determined by yeast assay from single frozen sections of trucut biopsies. Histological examination before p53 testing is essential to exclude cases where the p53 result may reflect only the status of the normal cells in the biopsy

Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein

The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy

Selective Pressures to Maintain Attachment Site Specificity of Integrative and Conjugative Elements

Integrative and conjugative elements (ICEs) are widespread mobile genetic elements that are usually found integrated in bacterial chromosomes. They are important agents of evolution and contribute to the acquisition of new traits, including antibiotic resistances. ICEs can excise from the chromosome and transfer to recipients by conjugation. Many ICEs are site-specific in that they integrate preferentially into a primary attachment site in the bacterial genome. Site-specific ICEs can also integrate into secondary locations, particularly if the primary site is absent. However, little is known about the consequences of integration of ICEs into alternative attachment sites or what drives the apparent maintenance and prevalence of the many ICEs that use a single attachment site. Using ICEBs1, a site-specific ICE from Bacillus subtilis that integrates into a tRNA gene, we found that integration into secondary sites was detrimental to both ICEBs1 and the host cell. Excision of ICEBs1 from secondary sites was impaired either partially or completely, limiting the spread of ICEBs1. Furthermore, induction of ICEBs1 gene expression caused a substantial drop in proliferation and cell viability within three hours. This drop was dependent on rolling circle replication of ICEBs1 that was unable to excise from the chromosome. Together, these detrimental effects provide selective pressure against the survival and dissemination of ICEs that have integrated into alternative sites and may explain the maintenance of site-specific integration for many ICEs.United States. Public Health Service (Grant GM050895