Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Expert evaluation of traffic signs: conventional vs. alternative designs

Traffic sign comprehension is significantly affected by their compliance with ergonomics design principles. Despite the UN Convention, designs vary among countries. The goal of this study was to establish theoretical and methodological bases for evaluating the design of conventional and alternative signs. Thirty-one conventional signs and 1–3 alternatives for each conventional sign were evaluated for their compliance with three ergonomics guidelines for sign design: physical and conceptual compatibility, familiarity and standardisation. Twenty-seven human factors and ergonomics experts from 10 countries evaluated the signs relative to their compliance with the guidelines. Analysis of variance across alternatives revealed that for 19 of the 31 signs, an alternative design received a significantly higher rating in its ergonomics design than the conventional sign with the same meaning. We also found a very high correlation between the experts’ ratings and comprehension from previous studies. In conclusion, many countries use signs for which better alternative designs exist, and therefore UN Convention signs should be re-examined, and ergonomics experts evaluation can serve as a good surrogate for road users’ comprehension surveys.

Practitioner summary: This study presents theoretical and methodological bases for evaluating the design of UN Conventional and alternative traffic signs. Human factors and ergonomics experts evaluated 31 conventional and 68 alternative road signs, based on ergonomics principles for sign design. Results indicated the need to re-examine poorly designed UN Convention signs.     

Bias against research on gender bias

The bias against women in academia is a documented phenomenon that has had detrimental consequences, not only for women, but also for the quality of science. First, gender bias in academia affects female scientists, resulting in their underrepresentation in academic institutions, particularly in higher ranks. The second type of gender bias in science relates to some findings applying only to male participants, which produces biased knowledge. Here, we identify a third potentially powerful source of gender bias in academia: the bias against research on gender bias. In a bibliometric investigation covering a broad range of social sciences, we analyzed published articles on gender bias and race bias and established that articles on gender bias are funded less often and published in journals with a lower Impact Factor than articles on comparable instances of social discrimination. This result suggests the possibility of an underappreciation of the phenomenon of gender bias and related research within the academic community. Addressing this meta-bias is crucial for the further examination of gender inequality, which severely affects many women across the world.     

Molecular Formation upon Ionization of van der Waals Clusters and Implication to Astrochemistry

The presence and formation of a large variety of organic molecules in the interstellar medium is evident from both astronomical data of absorption and emission bands at different regions of the spectrum. Specifically, polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the interstellar medium (ISM). The mechanism for their formation in ISM‘s low temperature environment is, as of yet, a mystery nonetheless. Understanding the mechanism of formation of complex molecules such as PAHs and nitrogen-based PAHs (PANH) in the ISM is a long-standing challenge which has been drawing a growing attention for the past several decades. In this review we wish to emphasize two things: Firstly, the essential role quantum chemistry can play in the study of astrochemical reactions. Secondly, we wish to demonstrate that said variety of possibilities for chemical reaction, starting upon ionization of van der Waals clusters. The potential for different chemical reactions to occur within a cluster environment arises from the fact that such processes can take place at low temperatures as the systems pose large amounts of energy upon ionization. Moreover, the spectator molecules in the cluster can provide a dissipation route for energy by detachment from the cluster, thus the system can stabilize efficiently even at low densities. The spectator molecules can also change the potential energy surface, by which it will pose a catalytic effect for certain reactions. We will demonstrate this by presenting Ab Initio Molecular Dynamic results on ionization of small acetylene clusters.     

Low-Frequency Ultrasound Effects on Intracellular Barriers in Nonviral Gene Delivery Processes

Gene therapy, the expression in cells of genetic material with therapeutic activity, has emerged as a promising approach for the treatment or prevention of human diseases. At the present time, major somatic gene-transfer approaches employ either viral or nonviral vectors. Nonviral vectors are less efficient at introducing and maintaining foreign gene expression, but have the profound advantage of being nonpathogenic and nonimmunogenic. In this study, we aimed to develop an efficient nonviral gene delivery system in which low-frequency ultrasound (LFUS) was applied to enhance gene expression of polyplexes formed with poly(2-dimethylaminoethyl methacrylate) and plasmid encoding for green fluorescent protein. Ultrasound (US), and in particular LFUS, can cause temporary membrane permeabilization and thereby enhance drug and gene entrance into viable cells. We evaluated possible additional favorable effects of LFUS on the polyplex transfection process, such as overcoming intracellular barriers. We found that pDMAEMA protected the plasmid DNA from ultrasonic degradation. Atomic force microscopy analysis also confirmed that the LFUS did not change the polyplexes’ morphology. We also attained an insight into the structure of polyplexes during LFUS exposure and found that LFUS induced a temporary partial detachment between the polymer chains and the plasmid. In addition, LFUS application on ovarian carcinoma cells transfected with the polyplexes induced a 27% enhancement in transfection efficiency. Based on these results, we propose that LFUS enhances the decomplexation of the polyplexes, and therefore, can be used to optimize transfection efficiency.     

A preliminary coupled MT-GA model for the prediction of highway runoff quality

Pollutants accumulated on road pavement during dry periods are washed off the surface with runoff water during rainfall events, presenting a potentially hazardous non-point source of pollution. Estimation of pollutant loads in these runoff waters is required for developing mitigation and management strategies, yet the numerous factors involved and their complex interconnected influences make straightforward assessment impossible. Data-driven models (DDMs) have lately been used in water and environmental research and have shown very good prediction ability. The proposed methodology of a coupled MT-GA (model tree-genetic algorithm) model provides an effective, accurate and easily calibrated predictive model for EMC (event mean concentration) of highway runoff pollutants. The models were trained and verified using a comprehensive data set of runoff events monitored in various highways in California, USA. EMCs of Cr, Pb, Zn, TOC and TSS were modeled, using different combinations of explanatory variables. The models' prediction ability in terms of correlation between predicted and actual values of both training and verification data was mostly higher than previously reported values. Sensitivity analysis was performed to examine the relative significance of each explanatory variable and the models' response to changes in input values.     

Social learning of an artificial fruit task in capuchin monkeys (Cebus apella).

Social learning in 11 human-raised capuchin monkeys (Cebus apella) was investigated using an artificial fruit that was designed as an analogue of natural foraging problems faced by primates. Each subject observed a human model open each of 3 principal components on the fruit in 1 of 2 alternative ways ("morphs"). The capuchin monkeys reproduced, to differing extents, the alternative techniques used for opening 1 component of the task (poking vs. pulling while twisting out a pair of smooth plastic bolts) but not the other 2. From the subjects' actions on the bolt latch, independent coders could recognize which morph they had witnessed, and they observed a degree of matching to the demonstrator's act consistent with simple imitation or object movement reenactment (A learns from watching B how an object, or parts of an object, move). Thus, these capuchins were capable of more complex social learning than has been recently ascribed to monkeys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Affective and cardiovascular effects of experimentally-induced social status.

Objective: Observational research suggests subordinate social status is associated with negative mental and physical health outcomes. However, observational studies have limitations, including confounding of social status with other factors, limited ability to infer causality, and difficulty of obtaining detailed affective and physiologic data. This study used experimental methods to test the hypothesis that subordinate social status per se causes psychological distress and cardiovascular arousal. Design: Forty-four women were randomly assigned to an induced subordinate or dominant status condition. Social status was manipulated using a procedure derived from status construction theory. Main Outcome Measures: Affective responses were assessed via self-report. Cardiovascular responses were assessed by measures of systolic and diastolic blood pressures obtained with an automated blood pressure machine. Results: Participants in the subordinate condition perceived themselves as lower in status; the reverse was true for dominant condition participants. Compared with induced dominant status, induced subordinate status produced increased negative affect and systolic blood pressure over the course of the study. Conclusion: Findings suggest social status can be experimentally manipulated and short-term induction of subordinate status can have adverse effects on affect and stress-related physiological systems. Results have implications for understanding how socioeconomic status "gets under the skin" to influence health. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Semantic and letter fluency in Spanish-English bilinguals.

Spanish-English bilinguals and English monolinguals completed 12 semantic, 10 letter, and 2 proper name fluency categories. Bilinguals produced fewer exemplars than monolinguals on all category types, but the difference between groups was larger (and more consistent) on semantic categories. Bilinguals and monolinguals produced the same number of errors across all category types. The authors discuss 2 accounts of the similarities and differences between groups and the interaction with category type, including (a) cross-language interference and (b) relatively weak connections in the bilingual lexical system because of reduced use of words specific to each language. Surprisingly, bilinguals' fluency scores did not improve when they used words in both languages. This result suggests that voluntary language switching incurs a processing cost. (PsycINFO Database Record (c) 2010 APA, all rights reserved)