Eco-friendly synthesis and study of new plant growth promoters: 3,3'-Diindolylmethane and its derivatives

3,3'-Diindolylmethane (DIM) derivatives 3a-k, prepared in one-pot from indoles 1a-k and hexamethylenetetramine (2) using ionic liquid [Bmim]BF(4) as eco-friendly recyclable solvent as well as catalyst, showed good plant growth promoting activity on Oryza sativa. Among the DIM derivatives synthesized 3c shows potent auxin like growth promoting activity.     

The Visual Priming of Motion-Defined 3D Objects

The perception of a stimulus can be influenced by previous perceptual experience, a phenomenon known as perceptual priming. However, there has been limited investigation on perceptual priming of shape perception of three-dimensional object structures defined by moving dots. Here we examined the perceptual priming of a 3D object shape defined purely by motion-in-depth cues (i.e., Shape-From-Motion, SFM) using a classic prime-target paradigm. The results from the first two experiments revealed a significant increase in accuracy when a “cloudy” SFM stimulus (whose object structure was difficult to recognize due to the presence of strong noise) was preceded by an unambiguous SFM that clearly defined the same transparent 3D shape. In contrast, results from Experiment 3 revealed no change in accuracy when a “cloudy” SFM stimulus was preceded by a static shape or a semantic word that defined the same object shape. Instead, there was a significant decrease in accuracy when preceded by a static shape or a semantic word that defined a different object shape. These results suggested that the perception of a noisy SFM stimulus can be facilitated by a preceding unambiguous SFM stimulus—but not a static image or a semantic stimulus—that defined the same shape. The potential neural and computational mechanisms underlying the difference in priming are discussed.     

2,2′-Diphenyl-3,3′-Diindolylmethane: A Potent Compound Induces Apoptosis in Breast Cancer Cells by Inhibiting EGFR Pathway

Despite recent advances in medicine, 30–40% of patients with breast cancer show recurrence underscoring the need for improved effective therapy. In this study, by in vitro screening we have selected a novel synthetic indole derivative 2,2''-diphenyl-3,3''-diindolylmethane (DPDIM) as a potential anti- breast cancer agent. DPDIM induces apoptosis both in vitro in breast cancer cells MCF7, MDA-MB 231 and MDA-MB 468 and in vivo in 7,12-dimethylbenz[α]anthracene (DMBA) induced Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show that DPDIM exerts apoptotic effect by negatively regulating the activity of EGFR and its downstream molecules like STAT3, AKT and ERK1/2 which are involved in the proliferation and survival of these cancer cells. In silico predictions also suggest that DPDIM may bind to EGFR at its ATP binding site. DPDIM furthermore inhibits EGF induced increased cell viability. We have also shown decreased expression of pro-survival factor Bcl-XL as well as increase in the level of pro-apoptotic proteins like Bax, Bad, Bim in DPDIM treated cells in vitro and in vivo. Our results further indicate that the DPDIM induced apoptosis is mediated through mitochondrial apoptotic pathway involving the caspase-cascade. To the best of our knowledge this is the first report of DPDIM for its anticancer activity. Altogether this report suggests that DPDIM could be an effective therapeutic agent for breast cancer.     

EGFR Mutation Testing in Patients with Advanced Non-Small Cell Lung Cancer: A Comprehensive Evaluation of Real-World Practice in an East Asian Tertiary Hospital

Introduction

Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea.

Methods

Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records.

Results

This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma.

Conclusions

In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.     

Effects of cleistanthins A and B on blood pressure and electrocardiogram in Wistar rats

We have studied the effects of cleistanthin A and cleistanthin B, phytoconstituents isolated from the leaves of Cleistanthus collinus Roxb. (Euphorbiaceae), on blood pressure, electrocardiogram, and barium chloride-induced arrhythmia in Wistar rats. The two compounds were isolated by column chromatography and their identity was confirmed spectroscopically. A healthy, male Wistar rat was used to record the invasive blood pressure and electrocardiograph. The antiarrhythmic effects of cleistanthins A and B were studied using the barium chloride model. Both cleistanthin A and cleistanthin B showed a dose-dependent hypotensive effect. Both compounds reduced the mean blood pressure significantly although the dose required for the effect was higher in the case of cleistanthin B. In the electrocardiogram, cleistanthins A and B significantly altered the electrical activity of the heart, the changes were transient and of no further consequence. Intravenous injection of 64 microg or more of cleistanthins A and B caused a sudden respiratory depression without affecting the electrocardiogram. Cleistanthins A and B did not display any antiarrhythmic effect against barium chloride-induced arrhythmia. In conclusion, both cleistanthin A and cleistanthin B exert a hypotensive effect and have no antiarrhythmic effect against barium chloride-induced arrhythmia in Wistar rats.     

Dopamine beta hydroxylase genotype identifies individuals less susceptible to bias in computer-assisted decision making

Computerized aiding systems can assist human decision makers in complex tasks but can impair performance when they provide incorrect advice that humans erroneously follow, a phenomenon known as "automation bias." The extent to which people exhibit automation bias varies significantly and may reflect inter-individual variation in the capacity of working memory and the efficiency of executive function, both of which are highly heritable and under dopaminergic and noradrenergic control in prefrontal cortex. The dopamine beta hydroxylase (DBH) gene is thought to regulate the differential availability of dopamine and norepinephrine in prefrontal cortex. We therefore examined decision-making performance under imperfect computer aiding in 100 participants performing a simulated command and control task. Based on two single nucleotide polymorphism (SNPs) of the DBH gene, -1041 C/T (rs1611115) and 444 G/A (rs1108580), participants were divided into groups of low and high DBH enzyme activity, where low enzyme activity is associated with greater dopamine relative to norepinephrine levels in cortex. Compared to those in the high DBH enzyme activity group, individuals in the low DBH enzyme activity group were more accurate and speedier in their decisions when incorrect advice was given and verified automation recommendations more frequently. These results indicate that a gene that regulates relative prefrontal cortex dopamine availability, DBH, can identify those individuals who are less susceptible to bias in using computerized decision-aiding systems.     

Ferrous iron oxidation by foam immobilized Acidithiobacillus ferrooxidans: Experiments and modeling

Ferrous iron bio‐oxidation by Acidithiobacillus ferrooxidans immobilized on polyurethane foam was investigated. Cells were immobilized on foams by placing them in a growth environment and fully bacterially activated polyurethane foams (BAPUFs) were prepared by serial subculturing in batches with partially bacterially activated foam (pBAPUFs). The dependence of foam density on cell immobilization process, the effect of pH and BAPUF loading on ferrous oxidation were studied to choose operating parameters for continuous operations. With an objective to have high cell densities both in foam and the liquid phase, pretreated foams of density 50 kg/m³ as cell support and ferrous oxidation at pH 1.5 to moderate the ferric precipitation were preferred. A novel basket‐type bioreactor for continuous ferrous iron oxidation, which features a multiple effect of stirred tank in combination with recirculation, was designed and operated. The results were compared with that of a free cell and a sheet‐type foam immobilized reactors. A fivefold increase in ferric iron productivity at 33.02 g/h/L of free volume in foam was achieved using basket‐type bioreactor when compared to a free cell continuous system. A mathematical model for ferrous iron oxidation by Acidithiobacillus ferrooxidans cells immobilized on polyurethane foam was developed with cell growth in foam accounted by an effectiveness factor. The basic parameters of simulation were estimated using the experimental data on free cell growth as well as from cell attachment to foam under nongrowing conditions. The model predicted the phase of both oxidation of ferrous in shake flasks by pBAPUFs as well as by fully activated BAPUFs for different cell loadings in foam. Model for stirred tank basket bioreactor predicted within 5% both transient and steady state of the experiments closely for the simulated dilution rates. Bio‐oxidation at high Fe²⁺ concentrations were simulated with experiments when substrate and product inhibition coefficients were factored into cell growth kinetics. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009