3D Microstructured Carbon Nanotube Electrodes for Trapping and Recording Electrogenic Cells

Electrogenic cells such as cardiomyocytes and neurons rely mainly on electrical signals for intercellular communication. Microelectrode arrays (MEAs) have been developed for long-term recording of cell signals and stimulation of electrogenic cells under low-cell-stress conditions, providing new insights in the behavior of electrogenic cells and the operation of the brain. To date, MEAs are relying on flat or needle-shaped electrode surfaces, mainly due to limitations in the lithographic processes. This paper relies on a previously reported elasto-capillary aggregation process to create 3D carbon nanotube (CNT) MEAs. This study shows that CNTs aggregate in well-shaped structures of similar size as cardiomyocytes are particularly interesting for MEA applications. This is because i) CNT microwells of the right diameter preferentially trap individual cardiomyocytes, which facilitates single cell recording without the need for clamping cells or signal deconvolution, and ii) once the cells are trapped inside of the CNT wells, this 3D CNT structure is used as an electrode surrounding the cell, which increases the cell-electrode contact area. As a result, this study finds that the recorded output voltages increase significantly (more than 200%). This fabrication process paves the way for future study of complex interactions between electrogenic cells and 3D recording electrodes.This work was supported by the Research Foundation—Flanders (FWO, Belgium) under Project No. 11S1214N. Michael De Volder was supported by the ERC Starting Grant (337739)—HIENA and the Marie Curie Grant CANA (618250). Davor Copic was supported by the Marie Curie Grant EmuCam (660351)

Factor copula models for item response data

Factor or conditional independence models based on copulas are proposed for multivariate discrete data such as item responses. The factor copula models have interpretations of latent maxima/minima (in comparison with latent means) and can lead to more probability in the joint upper or lower tail compared with factor models based on the discretized multivariate normal distribution (or multidimensional normal ogive model). Details on maximum likelihood estimation of parameters for the factor copula model are given, as well as analysis of the behavior of the log-likelihood. Our general methodology is illustrated with several item response data sets, and it is shown that there is a substantial improvement on existing models both conceptually and in fit to data

In-depth energy analysis of security algorithms and protocols for the Internet of Things

Computer Science

Do we still need animals? Surveying the role of animal-free models in Alzheimer’s and Parkinson’s disease research

The use of animals in neuroscience and biomedical research remains controversial. Policy is built around the “3R” principle of “Refining, Reducing and Replacing” animal experiments, and across the globe, different initiatives stimulate the use of animal-free methods. Based on an extensive literature screen to map the development and adoption of animal-free methods in Alzheimer's and Parkinson's disease research, we find that at least two in three examined studies rely on animals or on animal-derived models. Among the animal-free studies, the relative contribution of innovative models that may replace animal experiments is limited. We argue that the distinction between animal research and alternative models presents a false dichotomy, as the role and scientific value of both animal and animal-free approaches are intertwined. Calls to halt all animal experiments appear premature, as insufficient non-animal-based alternatives are available and their development lags behind. In light of this, we highlight the need for objective, unprejudiced monitoring, and more robust performance indicators of animal-free approaches

Amyloid beta oligomers induce neuronal elasticity changes in age-dependent manner: a force spectroscopy study on living hippocampal neurons

Small soluble species of amyloid-beta (Aβ) formed during early peptide aggregation stages are responsible for several neurotoxic mechanisms relevant to the pathology of Alzheimer's disease (AD), although their interaction with the neuronal membrane is not completely understood. This study quantifies the changes in the neuronal membrane elasticity induced by treatment with the two most common Aβ isoforms found in AD brains: Aβ40 and Aβ42. Using quantitative atomic force microscopy (AFM), we measured for the first time the static elastic modulus of living primary hippocampal neurons treated with pre-aggregated Aβ40 and Aβ42 soluble species. Our AFM results demonstrate changes in the elasticity of young, mature and aged neurons treated for a short time with the two Aβ species pre-aggregated for 2 hours. Neurons aging under stress conditions, showing aging hallmarks, are the most susceptible to amyloid binding and show the largest decrease in membrane stiffness upon Aβ treatment. Membrane stiffness defines the way in which cells respond to mechanical forces in their environment and has been shown to be important for processes such as gene expression, ion-channel gating and neurotransmitter vesicle transport. Thus, one can expect that changes in neuronal membrane elasticity might directly induce functional changes related to neurodegeneration

Identifying youth-friendly service practices associated with adolescents’ use of reproductive healthcare services in post-conflict Burundi: a cross-sectional study

BACKGROUND: Very little is known about reproductive health service (RHS) availability and adolescents’ use of these services in post-conflict settings. Such information is crucial for targeted community interventions that aim to improve quality delivery of RHS and outcomes in post-conflict settings. The objectives of this study therefore was to examine the density of RHS availability; assess spatial patterns of RHC facilities; and identify youth-friendly practices associated with adolescents’ use of services in post-conflict Burundi. METHODS: A cross-sectional survey was conducted from a full census of all facilities (n = 892) and provider interviews in Burundi. Surveyed facilities included all public, private, religious and community association owned-centers and hospitals. At each facility efforts were made to interview the officer-in-charge and a group of his/her staff. We applied both geospatial and non-spatial analyses, to examine the density of RHS availability and density, and to explore the association between youth-friendly practices and adolescents’ use of RHS in post-conflict Burundi. RESULTS: High spatial patterning of distances of RHC facilities was observed, with facilities clustered predominantly in districts exhibiting persistent violence. But, use of services remained undeterred. We further found a stronger association between use of RHS and facility and programming characteristics. Community outreach, designated check-in/exam rooms, educational materials (posters, print, and pictures) in waiting rooms, privacy and confidentiality were significantly associated with adolescents’ use of RHS across all facility types. Cost was associated with use only at religious facilities and youth involvement at private facilities. No significant association was found between provider characteristics and use of RHS at any facility. CONCLUSIONS: Our findings indicate the need to improve youth-friendly service practices in the provision of RHS to adolescents in Burundi and suggest that current approaches to provider training may not be adequate for improving these vital practices. Our mixed methods approach and results are generalizable to other countries and post-conflict settings. In post-conflict settings, the methods can be used to identify service availability and spatial patterns of RHC facilities to plan for targeted service interventions, to increase demand and uptake of services by youth and young adults

INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology

Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a screening strategy to detect cardiovascular liabilities, but there is room for further refinement. In this setting, we present the INSPIRE project, a European Training Network in safety pharmacology for Early Stage Researchers (ESRs), funded by the European Commission's H2020-MSCA-ITN programme. INSPIRE has recruited 15 ESR fellows that will conduct an individual PhD-research project for a period of 36 months. INSPIRE aims to be complementary to ongoing research initiatives. With this as a goal, an inventory of collaborative research initiatives in safety pharmacology was created and the ESR projects have been designed to be complementary to this roadmap. Overall, INSPIRE aims to improve cardiovascular safety evaluation, either by investigating technological innovations or by adding mechanistic insight in emerging safety concerns, as observed in the field of cardio-oncology. Finally, in addition to its hands-on research pillar, INSPIRE will organize a number of summer schools and workshops that will be open to the wider community as well. In summary, INSPIRE aims to foster both research and training in safety pharmacology and hopes to inspire the future generation of safety scientists

Does parallel item content on WOMAC's Pain and Function Subscales limit its ability to detect change in functional status?

BACKGROUND: Although the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) is considered the leading outcome measure for patients with osteoarthritis of the lower extremity, recent work has challenged its factorial validity and the physical function subscale's ability to detect valid change when pain and function display different profiles of change. This study examined the etiology of the WOMAC's physical function subscale's limited ability to detect change in the presence of discordant changes for pain and function. We hypothesized that the duplication of some items on the WOMAC's pain and function subscales contributed to this shortcoming. METHODS: Two eight-item physical function scales were abstracted from the WOMAC's 17-item physical function subscale: one contained activities and themes that were duplicated on the pain subscale (SIMILAR-8); the other version avoided overlapping activities (DISSIMILAR-8). Factorial validity of the shortened measures was assessed on 310 patients awaiting hip or knee arthroplasty. The shortened measures' abilities to detect change were examined on a sample of 104 patients following primary hip or knee arthroplasty. The WOMAC and three performance measures that included activity specific pain assessments – 40 m walk test, stair test, and timed-up-and-go test – were administered preoperatively, within 16 days of hip or knee arthroplasty, and at an interval of greater than 20 days following the first post-surgical assessment. Standardized response means were used to quantify change. RESULTS: The SIMILAR-8 did not demonstrate factorial validity; however, the factorial structure of the DISSIMILAR-8 was supported. The time to complete the performance measures more than doubled between the preoperative and first postoperative assessments supporting the theory that lower extremity functional status diminished over this interval. The DISSIMILAR-8 detected this deterioration in functional status; however, no significant change was noted for the SIMILAR-8. The WOMAC pain scale demonstrated a slight reduction in pain and the performance specific pain measures did not reflect a change in pain. All measures showed substantial improvement over the second assessment interval. CONCLUSIONS: These findings support the hypothesis that activity overlap on the pain and function subscales plays a causal role in limiting the WOMAC physical function subscale's ability to detect change

Positive feedback and noise activate the stringent response regulator Rel in mycobacteria

Phenotypic heterogeneity in an isogenic, microbial population enables a subset of the population to persist under stress. In mycobacteria, stresses like nutrient and oxygen deprivation activate the stress response pathway involving the two-component system MprAB and the sigma factor, SigE. SigE in turn activates the expression of the stringent response regulator, rel. The enzyme polyphosphate kinase 1 (PPK1) regulates this pathway by synthesizing polyphosphate required for the activation of MprB. The precise manner in which only a subpopulation of bacterial cells develops persistence, remains unknown. Rel is required for mycobacterial persistence. Here we show that the distribution of rel expression levels in a growing population of mycobacteria is bimodal with two distinct peaks corresponding to low (L) and high (H) expression states, and further establish that a positive feedback loop involving the mprAB operon along with stochastic gene expression are responsible for the phenotypic heterogeneity. Combining single cell analysis by flow cytometry with theoretical modeling, we observe that during growth, noise-driven transitions take a subpopulation of cells from the L to the H state within a "window of opportunity" in time preceding the stationary phase. We find evidence of hysteresis in the expression of rel in response to changing concentrations of PPK1. Our results provide, for the first time, evidence that bistability and stochastic gene expression could be important for the development of "heterogeneity with an advantage" in mycobacteria.Comment: Accepted for publication in PLoS On