Novel CDKL5 targets identified in human iPSC-derived neurons.

CDKL5 Deficiency Disorder (CDD) is a debilitating epileptic encephalopathy disorder affecting young children with no effective treatments. CDD is caused by pathogenic variants in Cyclin-Dependent Kinase-Like 5 (CDKL5), a protein kinase that regulates key phosphorylation events in neurons. For therapeutic intervention, it is essential to understand molecular pathways and phosphorylation targets of CDKL5.

Defining Biomarkers in Stem Cell-Derived Tissue Constructs for Drug and Disease Screening.

The development of stem cell-derived tissue constructs (SCTCs) for clinical applications, including regenerative medicine, drug and disease screening offers significant hope for detecting and treating intractable disorders. SCTCs display a variety of biomarkers that can be used to understand biological mechanisms, assess drug interactions, and predict disease. Although SCTCs can be derived from patients and share the same genetic make-up, they are nevertheless distinct from human patients in many significant ways, which can undermine the clinical significance of measurements in SCTCs.

Limitations in the electrochemical analysis of voltage transients.

. Chronopotentiometric voltage transients (VTs) are used to assess the performance of bionic electrodes. The data obtained from VTs are used to define the safe operating conditions of clinical devices.

Electrochemistry in a Two- or Three-Electrode Configuration to Understand Monopolar or Bipolar Configurations of Platinum Bionic Implants.

Electrodes are used in vivo for chemical sensing, electrophysiological recording, and stimulation of tissue. The electrode configuration used in vivo is often optimised for a specific anatomy and biological or clinical outcomes, not electrochemical performance. Electrode materials and geometries are constrained by biostability and biocompatibility issues and may be required to function clinically for decades.

CDKL5 deficiency disorder: molecular insights and mechanisms of pathogenicity to fast-track therapeutic development.

CDKL5 deficiency disorder (CDD) is an X-linked brain disorder of young children and is caused by pathogenic variants in the cyclin-dependent kinase-like 5 (CDKL5) gene. Individuals with CDD suffer infantile onset, drug-resistant seizures, severe neurodevelopmental impairment and profound lifelong disability. The CDKL5 protein is a kinase that regulates key phosphorylation events vital to the development of the complex neuronal network of the brain.

Investigating the feasibility and ethical implications of phenotypic screening using stem cell-derived tissue models to detect and manage disease.

Stem-cell-derived tissue models generated from sick people are being used to understand human development and disease, drug development, and drug screening. However, it is possible to detect disease phenotypes before a patient displays symptoms, allowing for their use as a disease screening tool. This raises numerous issues, some of which can be addressed using similar approaches from genetic screenings, while others are unique.

Comparison of the In Vitro and In Vivo Electrochemical Performance of Bionic Electrodes.

The electrochemical performance of platinum electrodes was assessed in vitro and in vivo to determine the impact of electrode implantation and the relevance of in vitro testing in predicting in vivo behaviour. A significant change in electrochemical response was seen after electrode polarisation. As a result, initial in vitro measurements were poor predictors of subsequent measurements performed in vitro or in vivo.

Restoring vision using optogenetics without being blind to the risks.

Retinit is pigmentosa is an incurable degenerative disease that causes loss of light-sensitive cells in the retina and leads to severe vision impairment. The development of optogenetics has created great hype around its potential to treat retinitis pigmentosa by the introduction of light-sensitive proteins into other neural cells in the retina. The first-in-human studies of optogenetic treatment for this disease have recently been reported (NCT02556736 and NCT03326336).

Fibrinogen, collagen, and transferrin adsorption to poly(3,4-ethylenedioxythiophene)-xylorhamno-uronic glycan composite conducting polymer biomaterials for wound healing applications.

We present the conducting polymer poly (3,4-ethylenedioxythiophene) (PEDOT) doped with an algal-derived glycan extract, Phycotrix™ [xylorhamno-uronic glycan (XRU84)], as an innovative electrically conductive material capable of providing beneficial biological and electrical cues for the promotion of favorable wound healing processes. Increased loading of the algal XRU84 into PEDOT resulted in a reduced surface nanoroughness and interfacial surface area and an increased static water contact angle. PEDOT-XRU84 films demonstrated good electrical stability and charge storage capacity and a reduced impedance relative to the control gold electrode.

Understanding charge transfer on the clinically used conical Utah electrode array: charge storage capacity, electrochemical impedance spectroscopy and effective electrode area.

. The Utah electrode is used for pre/clinical studies on neural recording and stimulation. Anecdotal and empirical reports on their performance have been made, resulting in variable testing methods.

Facile Development of a Fiber-Based Electrode for Highly Selective and Sensitive Detection of Dopamine.

A facile one-step method was used to create a selective and sensitive electrode for dopamine (DA) detection based upon a stainless steel (SS) filament substrate and reduced graphene oxide (rGO). The electrode successfully and selectively detects DA in the presence of uric acid and ascorbic acid without the need for a Nafion coating. The proposed electrode is easy to fabricate, low-cost, flexible, and strong.

Modeling Emergent Properties in the Brain Using Tissue Models to Investigate Neurodegenerative Disease.

Here we describe emergent properties of the brain and the key challenges associated with modelling them in vitro. Modeling emergent properties of the brain will provide insights into brain function, development, and disease.

Using Chronopotentiometry to Better Characterize the Charge Injection Mechanisms of Platinum Electrodes Used in Bionic Devices.

The safe charge injection capacity and charge density of neural stimulating electrodes is based on empirical evidence obtained from stimulating feline cortices. Stimulation induced tissue damage may be caused by electrochemical or biological mechanisms. Separating these mechanisms requires greater understanding of charge transfer at the electrode-tissue interface.

Predicting neural recording performance of implantable electrodes.

Recordings of neural activity can be used to aid communication, control prosthetic devices or alleviate disease symptoms. Chronic recordings require a high signal-to-noise ratio that is stable for years. Current cortical devices generally fail within months to years after implantation.

Measuring the effective area and charge density of platinum electrodes for bionic devices.

Objective: Neural stimulation is usually performed with fairly large platinum electrodes. Smaller electrodes increase the applied charge density, potentially damaging the electrode. Greater understanding of the charge injection mechanism is required for safe neural stimulation.