A phenotypic screening platform for chronic pain therapeutics using all-optical electrophysiology.

Chronic pain associated with osteoarthritis (OA) remains an intractable problem with few effective treatment options. New approaches are needed to model the disease biology and to drive discovery of therapeutics. We present an in vitro model of OA pain, where dorsal root ganglion (DRG) sensory neurons were sensitized by a defined mixture of disease-relevant inflammatory mediators, here called Sensitizing PAin Reagent Composition or SPARC.

Dual-sized hollow particle incorporated fibroin thermal insulating coatings on catheter for cerebral therapeutic hypothermia.

Selective endovascular hypothermia has been used to provide cooling-induced cerebral neuroprotection, but current catheters do not support thermally-insulated transfer of cold infusate, which results in an increased exit temperature, causes hemodilution, and limits its cooling efficiency. Herein, air-sprayed fibroin/silica-based coatings combined with chemical vapor deposited parylene-C capping film was prepared on catheter. This coating features in dual-sized-hollow-microparticle incorporated structures with low thermal conductivity.

Highly Parallelized, Multicolor Optogenetic Recordings of Cellular Activity for Therapeutic Discovery Applications in Ion Channels and Disease-Associated Excitable Cells.

Optogenetic assays provide a flexible, scalable, and information rich approach to probe compound effects for ion channel drug targets in both heterologous expression systems and associated disease relevant cell types. Despite the potential utility and growing adoption of optogenetics, there remains a critical need for compatible platform technologies with the speed, sensitivity, and throughput to enable their application to broader drug screening applications. To address this challenge, we developed the Swarm, a custom designed optical instrument for highly parallelized, multicolor measurements in excitable cells, simultaneously recording changes in voltage and calcium activities at high temporal resolution under optical stimulation.

Neural Adaptive Self-Triggered Control for Uncertain Nonlinear Systems With Input Hysteresis.

The issue of neural adaptive self-triggered tracking control for uncertain nonlinear systems with input hysteresis is considered. Combining radial basis function neural networks (RBFNNs) and adaptive backstepping technique, an adaptive self-triggered tracking control approach is developed, where the next trigger instant is determined by the current information. Compared with the event-triggered control mechanism, its biggest advantage is that it does not need to continuously monitor the trigger condition of the system, which is convenient for physical realization.

Correlation of Optical and Automated Patch Clamp Electrophysiology for Identification of Na1.7 Inhibitors.

The voltage-gated sodium channel Nav1.7 is a genetically validated target for pain; pharmacological blockers are promising as a new class of nonaddictive therapeutics. The search for Nav1.

Wild edible plants collected by Hani from terraced rice paddy agroecosystem in Honghe Prefecture, Yunnan, China.

Background: The Hani people in the Honghe Prefecture of Southeastern Yunnan, China, have practiced terraced rice paddy farming for more than 1300 years. These rice fields, combined with the surrounding forests and water systems, form a special agroecosystem that has attracted both tourists and scientists. For centuries, the local people have traditionally collected wild edible plants (WEP) from the agroecosystem, but this unique traditional practice in this area has never been reported.

All-Optical Electrophysiology for High-Throughput Functional Characterization of a Human iPSC-Derived Motor Neuron Model of ALS.

Human induced pluripotent stem cell (iPSC)-derived neurons are an attractive substrate for modeling disease, yet the heterogeneity of these cultures presents a challenge for functional characterization by manual patch-clamp electrophysiology. Here, we describe an optimized all-optical electrophysiology, "Optopatch," pipeline for high-throughput functional characterization of human iPSC-derived neuronal cultures. We demonstrate the method in a human iPSC-derived motor neuron (iPSC-MN) model of amyotrophic lateral sclerosis (ALS).

Optogenetic Approaches to Drug Discovery in Neuroscience and Beyond.

Recent advances in optogenetics have opened new routes to drug discovery, particularly in neuroscience. Physiological cellular assays probe functional phenotypes that connect genomic data to patient health. Optogenetic tools, in particular tools for all-optical electrophysiology, now provide a means to probe cellular disease models with unprecedented throughput and information content.

Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels.

Voltage-gated ion channels mediate electrical dynamics in excitable tissues and are an important class of drug targets. Channels can gate in sub-millisecond timescales, show complex manifolds of conformational states, and often show state-dependent pharmacology. Mechanistic studies of ion channels typically involve sophisticated voltage-clamp protocols applied through manual or automated electrophysiology.

Determination of oligosaccharides and monosaccharides in Hakka rice wine by precolumn derivation high-performance liquid chromatography.

This article presents a precolumn derivatization procedure with 1-phenyl-3-methyl-5-pyrazolone (PMP) reagent to detect oligosaccharides and monosaccharides in Hakka rice wine. The subsequent separation of the derivatized glucose-PMP also was performed using a mobile phase consisting of the molar ratio of acetonitrile to ammonium acetate buffer (0.1M) of 22:78 at a flow rate of 1.

Reporting sodium channel activity using calcium flux: pharmacological promiscuity of cardiac Nav1.5.

Voltage-gated sodium (Nav) channels are essential for membrane excitability and represent therapeutic targets for treating human diseases. Recent reports suggest that these channels, e.g.

Identification of novel small molecule modulators of K2P18.1 two-pore potassium channel.

Two-pore domain potassium (K2P) channels are responsible for background potassium (K+) current, which is crucial for the maintenance of resting membrane potential. K2P18.1, also called TWIK-related spinal cord K+ channel (TRESK) or KCNK18, is thought to be a major contributor to background K+ currents, particularly in sensory neurons where it is abundantly expressed.

Impaired neuropathic pain and preserved acute pain in rats overexpressing voltage-gated potassium channel subunit Kv1.2 in primary afferent neurons.

Voltage-gated potassium (Kv) channels are critical in controlling neuronal excitability and are involved in the induction of neuropathic pain. Therefore, Kv channels might be potential targets for prevention and/or treatment of this disorder. We reported here that a majority of dorsal root ganglion (DRG) neurons were positive for Kv channel alpha subunit Kv1.

A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons.

Neuropathic pain is a refractory disease characterized by maladaptive changes in gene transcription and translation in the sensory pathway. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the development of neuropathic pain is unclear. Here we identify a conserved lncRNA, named Kcna2 antisense RNA, for a voltage-dependent potassium channel mRNA, Kcna2, in first-order sensory neurons of rat dorsal root ganglion (DRG).

Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels.

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1-KCNEx complexes.

Calcium-activated chloride channel TMEM16A modulates mucin secretion and airway smooth muscle contraction.

Mucous cell hyperplasia and airway smooth muscle (ASM) hyperresponsiveness are hallmark features of inflammatory airway diseases, including asthma. Here, we show that the recently identified calcium-activated chloride channel (CaCC) TMEM16A is expressed in the adult airway surface epithelium and ASM. The epithelial expression is increased in asthmatics, particularly in secretory cells.

Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel.

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as I(Ks) and I(Kr). The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation.

[FI-KR non-separated method coupled with FAAS for the determination of Fe(II) and Fe(III) in water].

An FI-KR non-separated method coupled with FAAS for the determination of Fe(II) and Fe(III) was developed. With 60 s of sampling at a flow rate of 6.0 mL x min(-1), EF of 41 for Fe(III) and 9 for Fe(II) were obtained.

[Two steps elution method FI on-line adsorption and preconcentration coupled with FAAS for the determination of trace zinc].

A flow injection two steps elution method on-line sorption and preconcentration system coupled to flame atomic absorption spectrometry (FAAS) was developed for the determination of trace Zn in water samples. The conventional elution procedure was divided into two steps: elution procedure and detection procedure. During the elution procedure, the eluent was pumped into KR by the suction of the peristaltic pump and through PTFE tube instead of peristaltic pump tube.