Tailoring the Surface Chemistry of PEDOT:PSS to Promote Supported Lipid Bilayer Formation

This communication reports on a versatile and substrate-agnostic method to tune the surface chemistry of conducting polymers with the aim of bridging the chemical mismatch between bioelectronic devices and biological systems. As a proof of concept, the surface of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is grafted with a short-chain oligoethylene glycol monolayer to favor the formation of cell-derived supported lipid bilayers (SLBs). This method is tuned to optimize the affinity between the supported lipid bilayer and the conducting polymer, leading to significant improvements in bilayer quality and therefore electronic readouts. To validate the impact of surface functionalization on the system's ability to transduce biological phenomena into quantifiable electronic signals, the activity of a virus commonly used as a surrogate for SARS-CoV-2 (mouse hepatitis virus) is monitored with and without surface treatment. The functionalized devices exhibit significant improvements in electronic output, stemming from the improved SLB quality, therefore strengthening the case for the use of such an approach in membrane-on-a-chip systems

In Vivo Regulation of Glycogen Synthase Kinase-3β (GSK3β) by Serotonergic Activity in Mouse Brain

The goal of this study was to determine if serotonergic activity, which is impaired in depression, regulates the phosphorylation of glycogen synthase kinase-3β (GSK3β) in mouse brain in vivo. GSK3β is inhibited by phosphorylation on serine-9 and is a target of the mood stabilizer lithium. Following administration to mice of d-fenfluramine to stimulate serotonin (5HT) release and reduce its reuptake, and clorgyline to inhibit 5HT catabolism, levels of phospho-Ser9-GSK3β were 300–400% of control levels in the prefrontal cortex, hippocampus, and striatum. Treatment with monoamine reuptake inhibitors fluoxetine and imipramine also increased the level of phospho-Ser9-GSK3β. Using receptor selective agonists and antagonists, 5HT1A receptors were found to mediate increases, and 5HT2 receptors decreases, in phospho-Ser9-GSK3β levels. This indicates that serotonergic regulation of the phosphorylation of GSK3β is achieved by a balance between the opposing actions of these 5HT receptor subtypes. These findings demonstrate for the first time that serotonergic activity regulates the phosphorylation of GSK3β and show that this regulation occurs in mammalian brain in vivo. These results raise the possibility that impaired inhibitory control of GSK3β may occur in conditions where serotonergic activity is dysregulated, such as in mood disorders

Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression

Organisms have been exposed to the geomagnetic field (GMF) throughout evolutionary history. Exposure to the hypomagnetic field (HMF) by deep magnetic shielding has recently been suggested to have a negative effect on the structure and function of the central nervous system, particularly during early development. Although changes in cell growth and differentiation have been observed in the HMF, the effects of the HMF on cell cycle progression still remain unclear. Here we show that continuous HMF exposure significantly increases the proliferation of human neuroblastoma (SH-SY5Y) cells. The acceleration of proliferation results from a forward shift of the cell cycle in G1-phase. The G2/M-phase progression is not affected in the HMF. Our data is the first to demonstrate that the HMF can stimulate the proliferation of SH-SY5Y cells by promoting cell cycle progression in the G1-phase. This provides a novel way to study the mechanism of cells in response to changes of environmental magnetic field including the GMF

Modulating signaling networks by CRISPR/Cas9-mediated transposable element insertion

In a recent past, transposable elements (TEs) were referred to as selfish genetic components only capable of copying themselves with the aim of increasing the odds of being inherited. Nonetheless, TEs have been initially proposed as positive control elements acting in synergy with the host. Nowadays, it is well known that TE movement into host genome comprises an important evolutionary mechanism capable of increasing the adaptive fitness. As insights into TE functioning are increasing day to day, the manipulation of transposition has raised an interesting possibility of setting the host functions, although the lack of appropriate genome engineering tools has unpaved it. Fortunately, the emergence of genome editing technologies based on programmable nucleases, and especially the arrival of a multipurpose RNA-guided Cas9 endonuclease system, has made it possible to reconsider this challenge. For such purpose, a particular type of transposons referred to as miniature inverted-repeat transposable elements (MITEs) has shown a series of interesting characteristics for designing functional drivers. Here, recent insights into MITE elements and versatile RNA-guided CRISPR/Cas9 genome engineering system are given to understand how to deploy the potential of TEs for control of the host transcriptional activity.Fil: Vaschetto, Luis Maria Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; Argentin

Academic Performance and Behavioral Patterns

Identifying the factors that influence academic performance is an essential part of educational research. Previous studies have documented the importance of personality traits, class attendance, and social network structure. Because most of these analyses were based on a single behavioral aspect and/or small sample sizes, there is currently no quantification of the interplay of these factors. Here, we study the academic performance among a cohort of 538 undergraduate students forming a single, densely connected social network. Our work is based on data collected using smartphones, which the students used as their primary phones for two years. The availability of multi-channel data from a single population allows us to directly compare the explanatory power of individual and social characteristics. We find that the most informative indicators of performance are based on social ties and that network indicators result in better model performance than individual characteristics (including both personality and class attendance). We confirm earlier findings that class attendance is the most important predictor among individual characteristics. Finally, our results suggest the presence of strong homophily and/or peer effects among university students

Cognitive impairment and World Trade Centre-related exposures

On 11 September 2001 the World Trade Center (WTC) in New York was attacked by terrorists, causing the collapse of multiple buildings including the iconic 110-story ‘Twin Towers’. Thousands of people died that day from the collapse of the buildings, fires, falling from the buildings, falling debris, or other related accidents. Survivors of the attacks, those who worked in search and rescue during and after the buildings collapsed, and those working in recovery and clean-up operations were exposed to severe psychological stressors. Concurrently, these ‘WTC-affected’ individuals breathed and ingested a mixture of organic and particulate neurotoxins and pro-inflammogens generated as a result of the attack and building collapse. Twenty years later, researchers have documented neurocognitive and motor dysfunctions that resemble the typical features of neurodegenerative disease in some WTC responders at midlife. Cortical atrophy, which usually manifests later in life, has also been observed in this population. Evidence indicates that neurocognitive symptoms and corresponding brain atrophy are associated with both physical exposures at the WTC and chronic post-traumatic stress disorder, including regularly re-experiencing traumatic memories of the events while awake or during sleep. Despite these findings, little is understood about the long-term effects of these physical and mental exposures on the brain health of WTC-affected individuals, and the potential for neurocognitive disorders. Here, we review the existing evidence concerning neurological outcomes in WTC-affected individuals, with the aim of contextualizing this research for policymakers, researchers and clinicians and educating WTC-affected individuals and their friends and families. We conclude by providing a rationale and recommendations for monitoring the neurological health of WTC-affected individuals

Competing risk and heterogeneity of treatment effect in clinical trials

It has been demonstrated that patients enrolled in clinical trials frequently have a large degree of variation in their baseline risk for the outcome of interest. Thus, some have suggested that clinical trial results should routinely be stratified by outcome risk using risk models, since the summary results may otherwise be misleading. However, variation in competing risk is another dimension of risk heterogeneity that may also underlie treatment effect heterogeneity. Understanding the effects of competing risk heterogeneity may be especially important for pragmatic comparative effectiveness trials, which seek to include traditionally excluded patients, such as the elderly or complex patients with multiple comorbidities. Indeed, the observed effect of an intervention is dependent on the ratio of outcome risk to competing risk, and these risks – which may or may not be correlated – may vary considerably in patients enrolled in a trial. Further, the effects of competing risk on treatment effect heterogeneity can be amplified by even a small degree of treatment related harm. Stratification of trial results along both the competing and the outcome risk dimensions may be necessary if pragmatic comparative effectiveness trials are to provide the clinically useful information their advocates intend

The effectiveness of e-Learning on biosecurity practice to slow the spread of invasive alien species

Online e-Learning is increasingly being used to provide environmental training. Prevention measures including biosecurity are essential to reducing the introduction and spread of invasive alien species (IAS) and are central to international and national IAS policy. This paper is the first to evaluate the effectiveness of e-Learning as a tool to increase awareness, risk perception and biosecurity behaviour in relation to IAS among individuals conducting work activities or research (fieldwork) in the field. We surveyed participants (a mixture of students and professionals) before, and 6 months after undertaking an e-Learning course on IAS and biosecurity practices. Awareness of IAS and self-reported biosecurity behaviour increased after e-Learning among students and professionals. Students had a lower awareness of IAS than professionals before training (20% of students vs 60% of professionals), but after training students showed a greater increase in awareness which led to similar levels of awareness post-training (81%). Prior to training, risk perception was also lower amongst students than professionals (33% of students and 59% of professionals were aware of the risk that their activities posed to the accidental spread of IAS). There was no change in risk perception amongst professionals after training, however training led to a doubling of risk perception in students. E-Learning also led to an increase in reported biosecurity behaviour and cleaning practices and there were higher levels of biosecurity cleaning amongst professionals. The higher awareness and better biosecurity amongst professionals is likely to reflect their familiarity with the issues of IAS and day-to-day activities in the field. Our results suggest that e-Learning is an effective tool to raise awareness and encourage behaviour change among field workers and researchers in an attempt to reduce the risk of accidental introduction and spread of IAS

The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations. METHODS: Baboons were randomized into a breastfed (B) and four formula-fed groups: term, no DHA/ARA (T-); term, DHA/ARA supplemented (T+); preterm, no DHA/ARA (P-); preterm and DHA/ARA supplemented (P+). At four weeks adjusted age, brains were dissected and total fatty acids analyzed by gas chromatography and mass spectrometry. RESULTS: DHA and ARA are rich in many more structures than previously reported. They are most concentrated in structures local to the brain stem and diencephalon, particularly the basal ganglia, limbic regions, thalamus and midbrain, and comparatively lower in white matter. Dietary supplementation increased DHA in all structures but had little influence on ARA concentrations. Supplementation restored DHA concentrations to levels of breastfed neonates in all regions except the cerebral cortex and cerebellum. Prematurity per se did not exert a strong influence on DHA or ARA concentrations. CONCLUSION: 1) DHA and ARA are found in high concentration throughout the primate CNS, particularly in gray matter such as basal ganglia; 2) DHA concentrations drop across most CNS structures in neonates consuming formulas with no DHA, but ARA levels are relatively immune to ARA in the diet; 3) supplementation of infant formula is effective at restoring DHA concentration in structures other than the cerebral cortex. These results will be useful as a guide to future investigations of CNS function in the absence of dietary DHA and ARA