Survivin Mutant Protects Differentiated Dopaminergic SK-N-SH Cells Against Oxidative Stress

Oxidative stress is due to an imbalance of antioxidant/pro-oxidant homeostasis and is associated with the progression of several neurological diseases, including Parkinson's and Alzheimer's disease and amyotrophic lateral sclerosis. Furthermore, oxidative stress is responsible for the neuronal loss and dysfunction associated with disease pathogenesis. Survivin is a member of the inhibitors of the apoptosis (IAP) family of proteins, but its neuroprotective effects have not been studied. Here, we demonstrate that SurR9-C84A, a survivin mutant, has neuroprotective effects against H2O2-induced neurotoxicity. Our results show that H2O2 toxicity is associated with an increase in cell death, mitochondrial membrane depolarisation, and the expression of cyclin D1 and caspases 9 and 3. In addition, pre-treatment with SurR9-C84A reduces cell death by decreasing both the level of mitochondrial depolarisation and the expression of cyclin D1 and caspases 9 and 3. We further show that SurR9-C84A increases the antioxidant activity of GSH-peroxidase and catalase, and effectively counteracts oxidant activity following exposure to H2O2. These results suggest for the first time that SurR9-C84A is a promising treatment to protect neuronal cells against H2O2-induced neurotoxicity

A novel data-driven approach to examine children’s movements and social behaviour in schoolyard environments

Social participation at schoolyards is crucial for children's development. Yet, schoolyard environments contain features that can hinder children's social participation. In this paper, we empirically examine schoolyards to identify existing obstacles. Traditionally, this type of study requires huge amounts of detailed information about children in a given environment. Collecting such data is exceedingly difficult and expensive. In this study, we present a novel sensor data-driven approach for gathering this information and examining the effect of schoolyard environments on children's behaviours in light of schoolyard affordances and individual effectivities. Sensor data is collected from 150 children at two primary schools, using location trackers, proximity tags, and Multi-Motion receivers to measure locations, face-to-face contacts, and activities. Results show strong potential for this data-driven approach, as it allows collecting data from individuals and their interactions with schoolyard environments, examining the triad of physical, social, and cultural affordances in schoolyards, and identifying factors that significantly impact children's behaviours. Based on this approach, we further obtain better knowledge on the impact of these factors and identify limitations in schoolyard designs, which can inform schools, designers, and policymakers about current problems and practical solutions.Algorithms and the Foundations of Software technolog

Mixing characterisation for a serpentine microchannel equipped with embedded barriers

This paper describes the design, simulation, fabrication and experimental analysis of a passive micromixer for the mixing of biological solvents. The mixer consists of a T-junction, followed by a serpentine microchannel. the serpentine has three arcs, each equipped with circular barriers that are patterned as two opposing triangles. >The barriers are engineered to induce periodic perturbations in the flow field and enhance the mixing. CFD (Computational Fluid Dynamics) method is applied to optimise the geometric variables of the mixer before fabrication. The mixer is made from PDMS (Polydimethylsiloxane) using photo- and soft-lithography techniques. Experimental measurements are performed using yellow and blue food dyes as the mixing fluids. The mixing is measured by analysing the composition of the flow\u27s colour across the outlet channel. The performance of the mixer is examined in a wide range of flow rates from 0.5 to 10 µl/min. Mixing efficiencies of higher than 99.4% are obtained in the experiments confirming the results of numerical simulations. The proposed mixer can be employed as a part of lab-on-a-chip for biomedical applications

A glossary for research on human crowd dynamics

This article presents a glossary of terms that are frequently used in research on human crowds. This topic is inherently multidisciplinary as it includes work in and across computer science, engineering, mathematics, physics, psychology and social science, for example. We do not view the glossary presented here as a collection of finalised and formal definitions. Instead, we suggest it is a snapshot of current views and the starting point of an ongoing process that we hope will be useful in providing some guidance on the use of terminology to develop a mutual understanding across disciplines. The glossary was developed collaboratively during a multidisciplinary meeting. We deliberately allow several definitions of terms, to reflect the confluence of disciplines in the field. This also reflects the fact not all contributors necessarily agree with all definitions in this glossary

Divergent Modulation of Neuronal Differentiation by Caspase-2 and -9

Human Ntera2/cl.D1 (NT2) cells treated with retinoic acid (RA) differentiate towards a well characterized neuronal phenotype sharing many features with human fetal neurons. In view of the emerging role of caspases in murine stem cell/neural precursor differentiation, caspases activity was evaluated during RA differentiation. Caspase-2, -3 and -9 activity was transiently and selectively increased in differentiating and non-apoptotic NT2-cells. SiRNA-mediated selective silencing of either caspase-2 (si-Casp2) or -9 (si-Casp9) was implemented in order to dissect the role of distinct caspases. The RA-induced expression of neuronal markers, i.e. neural cell adhesion molecule (NCAM), microtubule associated protein-2 (MAP2) and tyrosine hydroxylase (TH) mRNAs and proteins, was decreased in si-Casp9, but markedly increased in si-Casp2 cells. During RA-induced NT2 differentiation, the class III histone deacetylase Sirt1, a putative caspase substrate implicated in the regulation of the proneural bHLH MASH1 gene expression, was cleaved to a ∼100 kDa fragment. Sirt1 cleavage was markedly reduced in si-Casp9 cells, even though caspase-3 was normally activated, but was not affected (still cleaved) in si-Casp2 cells, despite a marked reduction of caspase-3 activity. The expression of MASH1 mRNA was higher and occurred earlier in si-Casp2 cells, while was reduced at early time points during differentiation in si-Casp9 cells. Thus, caspase-2 and -9 may perform opposite functions during RA-induced NT2 neuronal differentiation. While caspase-9 activation is relevant for proper neuronal differentiation, likely through the fine tuning of Sirt1 function, caspase-2 activation appears to hinder the RA-induced neuronal differentiation of NT2 cells

Chimeric aptamers in cancer cell-targeted drug delivery

Aptamers are single-stranded structured oligonucleotides (DNA or RNA) that can bind to a wide range of targets ("apatopes") with high affinity and specificity. These nucleic acid ligands, generated from pools of random-sequence by an in vitro selection process referred to as systematic evolution of ligands by exponential enrichment (SELEX), have now been identified as excellent tools for chemical biology, therapeutic delivery, diagnosis, research, and monitoring therapy in real-time imaging. Today, aptamers represent an interesting class of modern Pharmaceuticals which with their low immunogenic potential mimic extend many of the properties of monoclonal antibodies in diagnostics, research, and therapeutics. More recently, chimeric aptamer approach employing many different possible types of chimerization strategies has generated more stable and efficient chimeric aptamers with aptamer-aptamer, aptamer-nonaptamer biomacromolecules (siRNAs, proteins) and aptamer-nanoparticle chimeras. These chimeric aptamers when conjugated with various biomacromolecules like locked nucleic acid (LNA) to potentiate their stability, biodistribution, and targeting efficiency, have facilitated the accurate targeting in preclinical trials. We developed LNA-aptamer (anti-nucleolin and EpCAM) complexes which were loaded in iron-saturated bovine lactofeerin (Fe-blf)-coated dopamine modified surface of superparamagnetic iron oxide (Fe3O4) nanoparticles (SPIONs). This complex was used to deliver the specific aptamers in tumor cells in a co-culture model of normal and cancer cells. This review focuses on the chimeric aptamers, currently in development that are likely to find future practical applications in concert with other therapeutic molecules and modalities

Traffic-adaptive duty cycle adaptation in TR-MAC protocol for wireless sensor networks

The Medium Access Control (MAC) layer can influence the energy consumption of a wireless sensor network (WSN) to a significant level. TR-MAC is an energy-efficient preamble sampling based MAC protocol for low power WSNs suitable for low data rate and low duty cycle scenario. However, low data rate is not always maintained in wireless sensor networks which often have to deal with event-driven scenarios where a sudden event rapidly increases traffic load within the network. In this paper we propose a traffic-adaptive duty cycle adaptation mechanism in order to provide responsiveness to traffic rate variations for TR-MAC protocol. This mechanism increases throughput and decreases packet delay while maintaining energy-efficiency without any extra information exchange among the sensor nodes in the network

Low power microwaves induce changes in gating function of Trpv4 ion channel proteins

Public exposure to electromagnetic radiation (EMR) emitted by radiofrequency (RF) and microwave (MW) technology devices such as mobile phones, Wi-Fi, smart meters and different medical equipment has increased significantly in the last decade. In response, the World Health Organisation (WHO) designed a research agenda that is based on the views of the leading international experts in RF bioeffect research. Research agenda items include animal and human studies, dosimetry and risk communication research, and in vitro mechanistic studies. A number of studies were undertaken to investigate biological and health effects of low-level exposures in the range of 900-2600 MHz (3G and 4G mobile networks). It was shown that RF-EMF can target cellular plasma membrane enzymes and receptors, and hence can control the cell function. RF radiation can also alter the intracellular calcium homoeostasis and consequently target the cell proliferation and differentiation as well as modify bioactivity of different enzymes. TRPV4 is a non-selective cation channel that is expressed in various tissues, including epithelial and endothelial cells, which can be activated by different stimuli such as heat, hypotonic stress, GSK1016790A, derivatives of arachidonic acids and shear stress. This study is aimed to evaluate the effects of MW radiation at 1800 MHz and power of 17dBm (47 V/m) on TRPP4 ion channel protein expressed in Hek-293 cells to better understanding of thermal/non-thermal nature of RF-EMF interaction with normal epithelial cells. Here, we used Ca+2 imaging and confocal microscopy to investigate the effects of RF/MW radiation at 1800 MHz and power of 17dBm on TRPV4 channel gating in response to its selective agonist GSK1016790A. We found that 4hrs exposure to MWs at 1800 MHz and 17dBm modulates the response of TRPV4 when compared to the control group