Evaluating a theory-based intervention for improving eHealth literacy in older adults: a single group, pretest–posttest design

All authors wish to express their gratitude to our participants for their enthusiastic participation in the intervention over a long five-week period. Also, all authors are deeply grateful to The National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning for their support (Grant No. NRF-2017R1C1B5017768).Background The Internet is considered an important channel for providing health information to older adults. We developed an intervention to improve eHealth literacy in older adults according to the information-motivation-behavioral skills (IMB) theory and Intervention Mapping. This study aimed to analyze the effect of a developed intervention on information, motivation, behavioral skills, and behaviors related to eHealth information in older adults. Methods Forty-six older adults over the age of 65 were recruited from two senior welfare centers in a city in South Korea. We divided the participants into four groups and conducted one intervention per group from March to December 2019. One intervention consisted of 5 sessions and was performed once a week (2 h/1 time) for 5 weeks, culminating in a total lecture time of 10 h. One lecture instructor and two assistant instructors supported the participants in the computer practices. Results Participants’ computer/web knowledge, perceived ease of use, perceived enjoyment, and attitude toward eHealth information showed statistically significant increases. The eHealth literacy efficacy score, searching performance score, and understanding score were also significantly increased. However, there was no significant difference in perceived usefulness. Conclusion The application of the current theory-based methodology can improve the quality of research in eHealth literacy. Additionally, various interventions should be developed and continuously applied to improve eHealth literacy among older adults.This work was supported by The National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning for their support (Grant No. NRF-2017R1C1B5017768)

ATAD5 restricts R-loop formation through PCNA unloading and RNA helicase maintenance at the replication fork

R-loops are formed when replicative forks collide with the transcriptional machinery and can cause genomic instability. However, it is unclear how R-loops are regulated at transcription-replication conflict (TRC) sites and how replisome proteins are regulated to prevent R-loop formation or mediate R-loop tolerance. Here, we report that ATAD5, a PCNA unloader, plays dual functions to reduce R-loops both under normal and replication stress conditions. ATAD5 interacts with RNA helicases such as DDX1, DDX5, DDX21 and DHX9 and increases the abundance of these helicases at replication forks to facilitate R-loop resolution. Depletion of ATAD5 or ATAD5-interacting RNA helicases consistently increases R-loops during the S phase and reduces the replication rate, both of which are enhanced by replication stress. In addition to R-loop resolution, ATAD5 prevents the generation of new R-loops behind the replication forks by unloading PCNA which, otherwise, accumulates and persists on DNA, causing a collision with the transcription machinery. Depletion of ATAD5 reduces transcription rates due to PCNA accumulation. Consistent with the role of ATAD5 and RNA helicases in maintaining genomic integrity by regulating R-loops, the corresponding genes were mutated or downregulated in several human tumors

Virtual reality-based monitoring test for MCI: A multicenter feasibility study

ObjectivesAs the significance of the early diagnosis of mild cognitive impairment (MCI) has emerged, it is necessary to develop corresponding screening tools with high ecological validity and feasible biomarkers. Virtual reality (VR)-based cognitive assessment program, which is close to the daily life of the older adults, can be suitable screening tools for MCI with ecological validity and accessibility. Meanwhile, dehydroepiandrosterone (DHEA) has been observed at a low concentration in the older adults with dementia or cognitive decline, indicating its potential as a biomarker of MCI. This study aimed to determine the efficacy and usability of a VR cognitive assessment program and salivary DHEA for screening MCI.MethodsThe VR cognitive assessment program and the traditional Montreal Cognitive Assessment (MOCA) test were performed on 12 patients with MCI and 108 healthy older adults. The VR program operates in a situation of caring for a grandchild, and evaluates the memory, attention, visuospatial, and executive functions. An analysis of covariance (ANCOVA), a partial correlation analysis, and receiving operating characteristic (ROC) curve analysis were conducted for statistical analysis.ResultsAccording to the ANCOVA, no significant difference in MOCA scores was found between the normal and MCI groups (F = 2.36, p = 0.127). However, the VR total score of the MCI group was significantly lower than that of the normal group (F = 8.674, p = 0.004). There was a significant correlation between the MOCA and VR scores in the total and matched subdomain scores. The ROC curve analysis also showed a larger area under the curve (AUC) for the VR test (0.765) than for the MOCA test (0.598), and the sensitivity and specificity of the VR program were 0.833 and 0.722, respectively. Salivary DHEA was correlated with VR total (R2 = 0.082, p = 0.01) and attention scores (R2 = 0.086, p = 0.009).ConclusionThe VR cognitive test was as effective as the traditional MOCA test in the MCI classification and safe enough for older adults to perform, indicating its potential as a diagnostic tool. It has also been shown that salivary DHEA can be used as a biomarker for MCI

Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Human ATAD5-RLC forms two distinct complexes functioning in PCNA unloading and Ub-PCNA de-ubiquitination.

Department of Biological Sciencesclos

Identification, Characterization, and Immobilization of an Organic Solvent-Stable Alkaline Hydrolase (PA27) from Pseudomonas aeruginosa MH38

An organic solvent-stable alkaline hydrolase (PA27) from Pseudomonas aeruginosa MH38 was expressed, characterized, and immobilized for biotechnological applications. Recombinant PA27 was expressed in Escherichia coli as a 27 kDa soluble protein and was purified by standard procedures. PA27 was found to be stable at pH 8–11 and below 50 °C. It maintained more than 80% of its activity under alkaline conditions (pH 8.0–11.0). Furthermore, PA27 exhibited remarkable stability in benzene and n-hexane at concentrations of 30% and 50%. Based on these properties, immobilization of PA27 for biotechnological applications was explored. Scanning electron microscopy revealed a very smooth spherical structure with numerous large pores. Interestingly, immobilized PA27 displayed improved thermal/chemical stabilities and high reusability. Specifically, immobilized PA27 has improved thermal stability, maintaining over 90% of initial activity after 1 h of incubation at 80 °C, whereas free PA27 had only 35% residual activity. Furthermore, immobilized PA27 showed higher residual activity than the free enzyme biocatalysts against detergents, urea, and phenol. Immobilized PA27 could be recycled 20 times with retention of ~60% of its initial activity. Furthermore, macroscopic hydrogel formation of PA27 was also investigated. These characteristics make PA27 a great candidate for an industrial biocatalyst with potential applications

Reduction of Potential-Induced-Degradation of p-Type PERC Solar Cell Modules by an Ion-Diffusion Barrier Layer Underneath the Front Glass

With the maturation of silicon-based technologies, silicon solar cells have achieved a high conversion efficiency that approaches the theoretical limit. Currently, great efforts are being made to enhance the reliability of silicon solar cells. When the silicon solar cells are made into modules, potential-induced-degradation (PID) occurs during operation because of the high voltage applied between the frame and the cells, which reduces the efficiency and output power. The diffusion of Na+ ions from the front glass and the increased leakage current along the migration path are the major causes of PID. In this work, atomic layer deposition (ALD)-grown amorphous thin Al2O3 layers are introduced underneath the front glass to prevent the diffusion of Na+ ions and the resulting PID. Accelerated PID tests showed that an ALD-grown Al2O3 layer of 30 nm could effectively suppress PID seriously affecting the conversion efficiency or light transmittance. The introduction of an ion-diffusion barrier underneath the front glass is expected to contribute to securing the long-term reliability of silicon-based electricity generation, together with the introduction of barrier layers inside the solar cells

Single Molecule Measurements Reveal Conformational Transitions During DNA Clamp Loading and Unloading

Proliferation cell nuclear antigen (PCNA) is a DNA clamp, playing an important role of providing a ??????platform?????? for various enzymes during DNA replication. The loading of the closed trimeric ring of PCNA into duplex DNA requires the ATP-dependent activity of replication factor C (RFC) complex. The unloading of PCNA from chromatin is crucial for the regulation of replication process and maintaining genomic stability and it was recently found that ATAD5 protein is complexed with RFC-like complex (RLC) to get involved in the unloading of PCNA. However, the molecular mechanisms of PCNA loading and unloading processes have remained poorly understood. Here, we report direct observation of the loading and unloading dynamics of human PCNA driven by RFC and ATAD5-RLC complexes, respectively, by single molecule fluorescence resonance energy transfer measurements. Distinct conformational stages during PCNA loading were clearly detected that represent open and closed conformations of PCNA trimer and another loading intermediate that possibly triggers the dissociation of RFC complex. The unloading of PCNA occurred upon binding ATAD5-RLC complex through an intermediate conformation, but not requiring the hydrolysis of ATP, which is later employed to recycle PCNA and ATAD5-RLC complexes. Our findings present a mechanistic model of the clamp loading/unloading dynamics and bring implications on the mechanism controlling the exclusive functions of RFC and ATAD5-RLC complexes in the loading and unloading processes, respectively. It further provides a platform to study how PCNA controls the exchange of various replication enzymes

Eukaryotic DNA replication: Orchestrated action of multi-subunit protein complexes

Genome duplication is an essential process to preserve genetic information between generations. The eukaryotic cell cycle is composed of functionally distinct phases: G1, S, G2, and M. One of the key replicative proteins that participate at every stage of DNA replication is the Mcm2-7 complex, a replicative helicase. In the G1 phase, inactive Mcm2-7 complexes are loaded on the replication origins by replication-initiator proteins, ORC and Cdc6. Two kinases, S-CDK and DDK, convert the inactive origin-loaded Mcm2-7 complex to an active helicase, the CMG complex in the S phase. The activated CMG complex begins DNA unwinding and recruits enzymes essential for DNA synthesis to assemble a replisome at the replication fork. After completion of DNA synthesis, the inactive CMG complex on the replicated DNA is removed from chromatin to terminate DNA replication. In this review, we will discuss the structure, function, and regulation of the molecular machines involved in each step of DNA replication