Highly Branched Poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) for High Performance Gene Transfection

The top-performing linear poly(β-amino ester) (LPAE), poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (C32), has demonstrated gene transfection efficiency comparable to viral-mediated gene delivery. Herein, we report the synthesis of a series of highly branched poly(5-amino-1-pentanol-co-1,4-butanediol diacrylate) (HC32) and explore how the branching structure influences the performance of C32 in gene transfection. HC32 were synthesized by an “A2 + B3 + C2” Michal addition strategy. Gaussia luciferase (Gluciferase) and green fluorescent protein (GFP) coding plasmid DNA were used as reporter genes and the gene transfection efficiency was evaluated in human cervical cancer cell line (HeLa) and human recessive dystrophic epidermolysis bullosa keratinocyte (RDEBK) cells. We found that the optimal branching structure led to a much higher gene transfection efficiency in comparison to its linear counterpart and commercial reagents, while preserving high cell viability in both cell types. The branching strategy affected DNA binding, proton buffering capacity and degradation of polymers as well as size, zeta potential, stability, and DNA release rate of polyplexes significantly. Polymer degradation and DNA release rate played pivotal parts in achieving the high gene transfection efficiency of HC32-103 polymers, providing new insights for the development of poly(β-amino ester)s-based gene delivery vectors

Aberrant hydroxymethylation of ANGPTL4 is associated with selective intrauterine growth restriction in monochorionic twin pregnancies

Selective intrauterine growth restriction (sIUGR) is a severe complication in monochorionic (MC) twin pregnancies, and it carries increased risks of poor prognosis. Current data suggest that vascular anastomoses and unequal placental sharing may be the key contributor to discordant foetal growth. While MC twins derive from a single zygote and have almost identical genetic information, the precise mechanisms remain unknown. DNA hydroxymethylation is a newly discovered epigenetic feature associated with gene regulation and modification. Here, we investigate discordant hydroxymethylation patterns between two placental shares of sIUGR and analyse the potential role of aberrant hydroxymethylation of angiopoietin-like 4 (ANGPTL4) in placental dysplasia. Hydroxymethylation DNA immunoprecipitation (hMeDIP)-chip and mRNA sequencing were performed to identify hydroxymethylation-associated genes. Real-time qPCR, western blotting, and immunohistochemistry were used to confirm ANGPTL4 expression. The mechanisms regulating ANGPTL4 were investigated by cell migration assay, invasion assay, viability assay, and apoptotic ratio assays, western blotting and hMeDIP-qPCR. Decreased ANGPTL4 was detected in the smaller placental shares of sIUGR. ANGPTL4 knockdown suppressed trophoblast invasiveness and migration, which possibly occurred through hypoxia inducible factor 1α (HIF-1α) and HIF-1 signalling pathway. Hypoxia leads to aberrant expression of ANGPTL4 and HIF-1α, positively correlated with their aberrant hydroxymethylation levels in promoter regions. Aberrant hydroxymethylation of ANGPTL4 may contribute to placental impairment by the HIF-1 signalling pathway in smaller placental shares of sIUGR

Data-driven heuristic dynamic programming with virtual reality

In this paper, we propose a virtual reality (VR) platform as a case study of machine learning, in this case applied to the goal representation heuristic dynamic programming (GrHDP) approach. In general, a VR platform normally includes a physical module, a control/learning module, and a VR module. It facilitates machine learning research, where scientists and engineers can participate in the simulation process to analyze dynamic experiments. The internal structure of the VR platform can be replaced according to different research targets, so the platform can be extended to other applications. In this paper, we present the detailed VR design strategy, with a number of applications, including a triple-link inverted pendulum balancing problem, a maze navigation problem, and a robot navigation with obstacle avoidance

Electroencephalogram γ-band activity during the perception of music key levels

An interdisciplinary research field, music perception involves various disciplines, such as psychology, neuroscience, and even physics. Research on music perception offers us a window into the mechanism of the brain. In music perception, the same distance of key shift in different directions tends to be perceived as different degrees of change. It, however, still remains unclear whether directional asymmetry is specific to key shift perception or a general phenomenon of key perception. Using both behavioral and electroencephalogram methods, this study examined Chinese nonmusicians' subjective ratings and electroencephalogram c-band activity related to a piece of music performed at three different key levels and presented in three separate performances, none of which contained a key shift. This study showed that directional asymmetry is a general phenomenon of key level perception rather than specific to key shift perception. Furthermore, a counterclockwisely modulated key is related to stronger γ-band spectral power than a clockwisely modulated key.4 page(s

Evaluation of PRGD/FK506/NGF conduits for peripheral nerve regeneration in rats

Context : Both tacrolimus (FK506) and nerve growth factor (NGF) enhance peripheral nerve regeneration, and in vitro experimental results demonstrate that the combination of FK506 and NGF increased neurite outgrowth compared with either treatment alone. Aim : To determine if the combination of FK506 and NGF benefits peripheral nerve regeneration compared with either treatment alone in vivo. Settings and Design : Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits. All of the 32 Wistar rats were randomly divided into 4 groups: Group A: RGD peptide modification of poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PRGD)/FK506/NGF; Group B: PRGD/FK506; Group C: PRGD/NGF; and Group D: autologous nerves. Materials and Methods : At 3 months after surgery, the regenerated rat sciatic nerve was evaluated by electrophysiology, calf triceps wet weight recovery rate, and histologic assessment. Statistical Analysis Used : The SPSS 10.0 software (Bizinsight, Beijing China) was used for statistical analysis. Results : The compound muscle action potentials (CMAPs) of groups A and D were significantly stronger than those of groups B and C. The calf triceps wet weight recovery rate of groups A and D were higher than those of groups B and C. The regenerated nerves of groups A and D were more mature than those of groups B and C. There was no significant difference between groups A and D. Conclusions : PRGD/FK506/NGF sustained-release nerve conduits are more effective in regenerating nerves than both PRGD/FK506 sustained-release nerve conduits and PRGD/NGF sustained-release nerve conduits. The effect is as good as that of an autograft

EEG evidence for directional asymmetry in Chinese nonmusicians' musical pitch perception

The same amount of musical pitch change in different directions may be perceived as different degrees of change, such that the clockwise modulation has a shorter psychological distance from the original music than the counterclockwise modulation does. However, the finding of directional asymmetry is largely based on behavioral studies. It is unclear whether it has its electrophysiological basis. The current study examines the electrophysiological basis of directional asymmetry. Using EEG, this study examines human brain activities when listening to musical stimuli with systematically different pitch levels. The results demonstrate electrophysiological evidence for directional asymmetry by showing that the counterclockwise transposition elicited larger brain activities than the clockwise transposition. Furthermore, by testing adult nonmusicians speaking a tonal language, namely Chinese, the current study supports the universality of the finding of right hemisphere dominance of musical pitch perception, despite the previous finding that Chinese lexical tones are primarily processed in the left hemisphere.4 page(s

Role of Osteoprotegerin and Its Gene Polymorphisms in the Occurrence of Left Ventricular Hypertrophy in Essential Hypertensive Patients

Overall view from N. Grand Avenue, looking southwest; Dorothy Chandler Pavilion at left; A 739-seat thrust stage at the Los Angeles Music Center designed by Welton Becket and Associates. The smallest of the three venues, the Taper is flanked by the Dorothy Chandler Pavilion and the Ahmanson Theatre on the Music Center Plaza. Mr. Becket designed the center in the style of New Formalism, which emphasized geometric shapes. The perfectly circular Taper is considered one of his best works, featuring a distinctive decorated drum of a design with its exterior wrapped in a lacy precast relief by Jacques Overhoff. The lobby has a curving, abalone wall by Tony Duquette. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 7/29/2013