Differences in the Relative Abundance of ProBDNF and Mature BDNF in A549 and H1299 Human Lung Cancer Cell Media

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has been linked to several human malignancies and shown to promote tumorigenesis. The purpose of this study was to explore the relative abundance of pro-brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) in A549 (p53 wild-type) and H1299 (p53-null) lung cancer cell media. Higher levels of proBDNF were detected in the media of A549 cells than in H1299 cell media. Using inhibitors, we found that the levels of proBDNF and mBDNF in the media are likely regulated by PI3K, AKT, and NFκB. However, the largest change in these levels resulted from MMP2/9 inhibition. Blocking p53 function in A549 cells resulted in increased mBDNF and decreased proBDNF, suggesting a role for p53 in regulating these levels. The ratio of proBDNF/mBDNF was not affected by MMP2 knockdown but increased in the media of both cell lines upon knockdown of MMP9. Downregulation of either MMP2 or MMP9 by siRNA showed that MMP9 siRNA treatment of either A549 or H1299 cells resulted in decreased cell viability and increased apoptosis, an effect diminished upon the same treatment with proBDNF immunodepleted media, suggesting that MMP9 regulates the cytotoxic effects induced by proBDNF in lung cancer cells.     

Surface degradation and nanoparticle release of a commercial nanosilica/polyurethane coating under UV exposure

Many coating properties such as mechanical, electrical, and ultraviolet (UV) resistance are greatly enhanced by the addition of nanoparticles, which can potentially increase the use of nanocoatings for many outdoor applications. However, because polymers used in all coatings are susceptible to degradation by weathering, nanoparticles in a coating may be brought to the surface and released into the environment during the life cycle of a nanocoating. Therefore, the goal of this study is to investigate the process and mechanism of surface degradation and potential particle release from a commercial nanosilica/polyurethane coating under accelerated UV exposure. Recent research at the National Institute of Standards and Technology (NIST) has shown that the matrix in an epoxy nanocomposite undergoes photodegradation during exposure to UV radiation, resulting in surface accumulation of nanoparticles and subsequent release from the composite. In this study, specimens of a commercial polyurethane (PU) coating, to which a 5 mass% surface-treated silica nanoparticle solution was added, were exposed to well-controlled, accelerated UV environments. The nanocoating surface morphological changes and surface accumulation of nanoparticles as a function of UV exposure were measured, along with chemical change and mass loss using a variety of techniques. Particles from the surface of the coating were collected using a simulated rain process developed at NIST, and the collected runoff specimens were measured using inductively coupled plasma optical emission spectroscopy to determine the amount of silicon released from the nanocoatings. The results demonstrated that the added silica nanoparticle solution decreased the photodegradation rate (i.e., stabilization) of the commercial PU nanocoating. Although the degradation was slower than the previous nanosilica epoxy model system, the degradation of the PU matrix resulted in accumulation of silica nanoparticles on the nanocoating surface and release to the environment by simulated rain. These experimental data are valuable for developing models to predict the long-term release of nanosilica from commercial PU nanocoatings used outdoors and, therefore, are essential for assessing the health and environmental risks during the service life of exterior PU nanocoatings.     

Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3–36)

Vitamin B₁₂–peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B₁₂ (B₁₂). There remains a lack of structural studies investigating the effects of B₁₂ conjugation on peptide secondary structure. Determining the solution structure of a B₁₂–peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B₁₂ conjugates of the anorectic peptide PYY(3–36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3–36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B₁₂ conjugates and validates the fact that B₁₂ can be conjugated to a peptide without markedly affecting peptide secondary structure.     

Metformin Reduces Lipogenesis Markers in Obese Mice Fed a Low-Carbohydrate and High-Fat Diet

Lipogenesis is the process by which fatty acids are synthesized. In metabolic syndrome, an insulin resistant state along with high plasma levels of free fatty acids (FFA) and hyperglycemia may contribute to the lipogenic process. The aim of the present study was to investigate the effects of oral administration of metformin on the expression of lipogenic genes and glycemic profile in mice fed with low‐carbohydrate high‐fat diet by evaluating their metabolic profile. SWISS male mice were divided into 4 groups (N = 7) that were fed with standard (ST), standard plus metformin (ST + MET), low‐carbohydrate high‐fat diet (LCHFD) and low‐carbohydrate high‐fat diet plus metformin (LCHFD + MET) (100 mg kg^?1 diet) diets respectively. Food intake, body weight and blood parameters, such as glucose tolerance, insulin sensitivity, glucose, HDL‐c, total cholesterol, triglycerides, ASL and ALT levels were assessed. Histological analyses were performed on hematoxylin and eosin‐stained epididymal adipose tissue histological specimens. The expression levels of peroxisome proliferator‐activated receptor (PPARγ), sterol regulatory element‐binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl‐CoA carboxylase (ACC), were assessed by RT‐PCR. This study showed that metformin decreased adipocyte area, body weight and food consumption in obese animals when compared to the standard group. Furthermore, the expression of lipogenic markers in adipose tissue were diminished in obese animals treated with metformin. This data showed that oral administration of metformin improved glucose and lipid metabolic parameters in white adipose tissue by reducing the expression of lipogenesis markers, suggesting an important clinical application of MET in treating obesity‐related diseases in metabolic syndrome.     

Why are rocks pointy? Children's preference for teleological explanations of th natural world.

Teleological explanations are based on the assumption that an object or behavior exists for a purpose. Two studies explored the tendency of adults and first-, second-, and fourth-grade elementary-school children to explain the properties of living and nonliving natural kinds in teleological terms. Consistent with the hypothesis that young children possess a promiscuous teleological tendency, Study 1 found that children were more likely than adults to broadly examine the properties of both living and nonliving natural kinds in teleological terms, although the kinds of functions that they endorsed varied with age. Study 2 was an attempt to reduce children's broad teleological bias by introducing a pretrial that described, in nonteleological terms, the physical process by which nonliving natural kinds form. In spite of this attempt, Study 2 replicated the effects of Study 1, with only fourth graders showing any shift in preference for teleological explanation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of the reinforcing and anxiogenic effects of intravenous cocaine.

People report that ethanol improves the experience produced by cocaine. This effect may be attributable to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. To test this, rats were trained to run an alley for a single intravenous dose of either cocaine (0.5–2.0 mg/kg) or an equimolar dose of CE (0.75–2.88 mg/kg). The rats' start latency and running speed measured the reinforcing effects of the drugs and the number of times rats approached but failed to enter the goal box (i.e., approach-avoidance retreats) indexed anxiety. Rats reinforced with CE had shorter start latencies and faster running speeds and exhibited fewer "retreats" than cocaine-reinforced rats. These results suggest that CE is more reinforcing and less anxiogenic than cocaine and hence may account for the combined effects of cocaine and ethanol in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Performance Measurement of Training in Engineering Organizations

This work introduces a new training program performance assessment methodology for engineering organizations that is based upon needs assessment, types of training, and training effectiveness measures. The methodology checks whether predefined objectives of a company are identified through a needs assessment. Effectiveness is judged on whether the types of training and coursework content are formulated to fulfill the needs assessment objectives, whether the coursework is available to the proper employees, whether the courses are attended and understood by the employees, and whether the coursework content is utilized in the work place to meet the needs assessment objectives of the company. A case study of three training programs conducted within a public sector engineering organization is included to demonstrate the methodology and evaluate both the three programs and the methodology effectiveness. Conclusions suggest improvements to future training programs for the public sector engineering organization, as well as describe potential enhancements to the effectiveness measures of the methodology that can be recognized through further study of existing training programs.     

Nature and nature in psychology.

This article explores the meanings of nature, and examines how understandings of this term inform the field of psychology. In this period of high, late, or post-modernity, many of the "givens" become contested, and perhaps nothing has become more contested than nature itself. There is a threefold purpose to this paper. This first goal is to unravel two types of nature in psychology, to be distinguished as nature and Nature. The second aim is to discuss how these types of nature/Nature have been distinguished epistemologically, ontologically and methodologically within the field. The final purpose is to suggest points of unity within nature and Nature in psychology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)