Human iN neuronal model of schizophrenia displays dysregulation of chromogranin B and related neuropeptide transmitter signatures.

Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of neurotransmitters released to mediate cell-cell communication which are essential to brain functions in health and disease. We hypothesized that SZ may involve dysregulation of neurotransmitters secreted from neurons. To gain an understanding of human SZ, induced neurons (iNs) were derived from SZ patients and healthy control subjects to investigate peptide neurotransmitters, known as neuropeptides, which represent the major class of transmitters. The iNs were subjected to depolarization by high KCl in the culture medium and the secreted neuropeptides were identified and quantitated by nano-LC-MS/MS tandem mass spectrometry. Several neuropeptides were identified from schizophrenia patient-derived neurons, including chromogranin B (CHGB), neurotensin, and natriuretic peptide. Focusing on the main secreted CHGB neuropeptides, results revealed differences in SZ iNs compared to control iN neurons. Lower numbers of distinct CHGB peptides were found in the SZ secretion media compared to controls. Mapping of the peptides to the CHGB precursor revealed peptides unique to either SZ or control, and peptides common to both conditions. Also, the iNs secreted neuropeptides under both KCl and basal (no KCl) conditions. These findings are consistent with reports that chromogranin B levels are reduced in the cerebrospinal fluid and specific brain regions of SZ patients. These findings suggest that iNs derived from SZ patients can model the decreased CHGB neuropeptides observed in human SZ.

Surface Reorganization of Transition Metal Dichalcogenide Nanoflowers for Efficient Electrochemical Coenzyme Regeneration.

In the past 20 years, enzymatic conversions have been intensely examined as a practical and environmentally friendly alternative to traditional organocatalytic conversions for chemicals and pharmaceutical intermediate production. Out of all commercial enzymes, more than one-fourth are oxidoreductases that operate in tandem with coenzymes, typically nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH). Enzymes utilize coenzymes as a source for electrons, protons, or holes. Unfortunately, coenzymes can be exorbitant; thus, recycling coenzymes is paramount to establishing a sustainable and affordable cell-free enzymatic catalyst system. Herein, cost-effective transition metal dichalcogenides (TMDCs), 2H-MoS2, 2H-WS2, and 2H-WSe2, were employed for the first time for direct electrochemical reduction of NAD+ to the active form of the NADH (1,4-NADH). Of the three TMDCs, 2H-WSe2 shows optimal activity, producing 1,4 NADH at a rate of 6.5 µmol cm-2 h-1 and a faradaic efficiency of 45% at -0.8 V vs Ag/AgCl. Interestingly, a self-induced surface reorganization process was identified, where the native surface oxide grown in the air was spontaneously removed in the electrochemical process, resulting in the activation of TMDCs.

Improved performance of micro-fabricated preconcentrators using silica nanoparticles as a surface template.

A new approach of enhancing the adsorption capability of the widely used polymer adsorbent Tenax TA poly(2,6-diphenylene oxide) through its deposition on a nano-structured template is reported. The modified Tenax TA-coated silica nanoparticles (SNP) are incorporated as an adsorbent bed in silicon based micro-thermal preconcentrator (µTPC) chips with an array of square microposts embedded inside the cavity and sealed with a Pyrex cover. The interior surface of the chip is first modified by depositing SNP using a layer-by-layer self-assembly technique followed by coating with Tenax TA. The adsorption capacity of the SNP-Tenax TA µTPC is enhanced by as much as a factor of three compared to the one coated solely with thin film Tenax TA for the compounds tested. The increased adsorption ability of the Tenax TA is attributed to the higher surface area provided by the underlying porous SNP coating and the pores between SNPs affecting the morphology of deposited Tenax TA film by bringing nano-scale features into the polymer. In addition, the adsorption ability of the SNP coating as a pseudo-selective inorganic adsorption bed for polar compounds was also observed. The modified Tenax TA-coated SNP µTPC is a promising development toward integrated micro-gas chromatography systems.