Possible Role of Correlation Coefficients and Network Analysis of Multiple Intracellular Proteins in Blood Cells of Patients with Bipolar Disorder in Studying the Mechanism of Lithium Responsiveness: A Proof-Concept Study.

The mechanism of lithium treatment responsiveness in bipolar disorder (BD) remains unclear. The aim of this study was to explore the utility of correlation coefficients and protein-to-protein interaction (PPI) network analyses of intracellular proteins in monocytes and CD4 lymphocytes of patients with BD in studying the potential mechanism of lithium treatment responsiveness. Patients with bipolar I or II disorder who were diagnosed with the MINI for DSM-5 and at any phase of the illness with at least mild symptom severity and received lithium (serum level ≥ 0.

Cell-type specific molecular expression levels by restricted-dimensional cytometry.

Background: Cytometric analysis has been commonly used to delineate distinct cell subpopulations among peripheral blood mononuclear cells by the differential expression of surface receptors. This capability has reached its apogee with high-dimensional approaches such as mass cytometry and spectral cytometry that include simultaneous assessment of 20-50 analytes. Unfortunately, this approach also engenders significant complexity with analytical and interpretational pitfalls.

Differences in intracellular protein levels in monocytes and CD4 lymphocytes between bipolar depressed patients and healthy controls: A pilot study with tyramine-based signal-amplified flow cytometry.

Background: Molecular biomarkers for bipolar disorder (BD) that distinguish it from other manifestations of depressive symptoms remain unknown. The aim of this study was to determine if a very sensitive tyramine-based signal-amplification technology for flow cytometry (CellPrint™) could facilitate the identification of cell-specific analyte expression profiles of peripheral blood cells for bipolar depression (BPD) versus healthy controls (HCs).

Methods: The diagnosis of psychiatric disorders was ascertained with Mini International Neuropsychiatric Interview for DSM-5.

Divergent Directionality of Immune Cell-Specific Protein Expression between Bipolar Lithium Responders and Non-Responders Revealed by Enhanced Flow Cytometry.

: There is no biomarker to predict lithium response. This study used ™ enhanced flow cytometry to study 28 proteins representing a spectrum of cellular pathways in monocytes and CD4 lymphocytes before and after lithium treatment in patients with bipolar disorder (BD). : Symptomatic patients with BD type I or II received lithium (serum level ≥ 0.

Protein Biomarkers in Monocytes and CD4 Lymphocytes for Predicting Lithium Treatment Response of Bipolar Disorder: a Feasibility Study with Tyramine-Based Signal-Amplified Flow Cytometry.

Purpose: To determine if enhanced flow cytometry () can identify intracellular proteins of lithium responsiveness in monocytes and CD4 lymphocytes from patients with bipolar disorder.

Methods: Eligible bipolar I or II patients were openly treated with lithium for 16-weeks. Baseline levels of Bcl2, BDNF, calmodulin, Fyn, phospho-Fyn/phospho-Yes, GSK3β, phospho-GSK3αβ, HMGB1, iNOS, IRS2, mTor, NLPR3, PGM1, PKA C-α, PPAR-γ, phospho-RelA, and TPH1 in monocytes and CD4 lymphocytes of lithium responders and non-responders were measured with .

Primary Care Behavioral Health Integration: Promoting the Quadruple Aim.

Chronic medical and common behavioral health conditions have been shown to benefit from team-based care approaches that include integrated behavioral health providers. Team-based integrated care can promote the Quadruple Aim, encompassing health care outcomes, patient satisfaction, provider work/life experience, and the cost of care.

Deconvolution of Raman spectroscopic signals for electrostatic, H-bonding, and inner-sphere interactions between ions and dimethyl phosphate in solution.

Quantitative analysis of metal ion-phosphodiester interactions is a significant experimental challenge due to the complexities introduced by inner-sphere, outer-sphere (H-bonding with coordinated water), and electrostatic interactions that are difficult to isolate in solution studies. Here, we provide evidence that inner-sphere, H-bonding and electrostatic interactions between ions and dimethyl phosphate can be deconvoluted through peak fitting in the region of the Raman spectrum for the symmetric stretch of non-bridging phosphate oxygen (ν(s)PO(2)(-)). An approximation of the change in vibrational spectra due to different interaction modes is achieved using ions capable of all or a subset of the three forms of metal ion interaction.

A quantitative Raman spectroscopic signal for metal-phosphodiester interactions in solution.

Accurate identification and quantification of metal ion-phosphodiester interactions are essential for understanding the role of metal ions as determinants of three-dimensional folding of large RNAs and as cofactors in the active sites of both RNA and protein phosphodiesterases. Accomplishing this goal is difficult due to the dynamic and complex mixture of direct and indirect interactions formed with nucleic acids and other phosphodiesters in solution. To address this issue, Raman spectroscopy has been used to measure changes in bond vibrational energies due to metal interactions.

Detection of innersphere interactions between magnesium hydrate and the phosphate backbone of the HDV ribozyme using Raman crystallography.

A Raman microscope and Raman difference spectroscopy are used to detect the vibrational signature of RNA-bound magnesium hydrate in crystals of hepatitis delta virus (HDV) ribozyme and to follow the effects of magnesium hydrate binding to the nonbridging phosphate oxygens in the phosphodiester backbone. There is a correlation between the Raman intensity of the innersphere magnesium hydrate signature peak, near 322 cm-1, and the intensity of the PO2- symmetric stretch, near 1100 cm-1, perturbed by magnesium binding, demonstrating direct observation of -PO2-..

RNA-dependent folding and stabilization of C5 protein during assembly of the E. coli RNase P holoenzyme.

The pre-tRNA processing enzyme ribonuclease P is a ribonucleoprotein. In Escherichia coli assembly of the holoenzyme involves binding of the small (119 amino acid residue) C5 protein to the much larger (377 nucleotide) P RNA subunit. The RNA subunit makes the majority of contacts to the pre-tRNA substrate and contains the active site; however, binding of C5 stabilizes P RNA folding and contributes to high affinity substrate binding.

The pre-tRNA nucleotide base and 2'-hydroxyl at N(-1) contribute to fidelity in tRNA processing by RNase P.

Fidelity in tRNA processing by the RNase P RNA from Escherichia coli depends, in part, on interactions with the nucleobase and 2' hydroxyl group of N(-1), the nucleotide immediately upstream of the site of RNA strand cleavage. Here, we report a series of biochemical and structure-function studies designed to address how these interactions contribute to cleavage site selection. We find that simultaneous disruption of cleavage site nucleobase and 2' hydroxyl interactions results in parallel reactions leading to correct cleavage and mis-cleavage one nucleotide upstream (5') of the correct site.

Recent insights into the structure and function of the ribonucleoprotein enzyme ribonuclease P.

In bacteria, the tRNA-processing endonuclease ribonuclease P is composed of a large ( approximately 400 nucleotide) catalytic RNA and a smaller ( approximately 100 amino acid) protein subunit that is essential for substrate recognition. Current biochemical and biophysical investigations are providing fresh insights into the modular architecture of the ribozyme, the mechanisms of substrate specificity and the role of essential metal ions in catalysis. Together with recent high-resolution structures of portions of the ribozyme, these findings are beginning to reveal how the functions of RNA and protein are coordinated in this ribonucleoprotein enzyme.

Recognition of the 5' leader of pre-tRNA substrates by the active site of ribonuclease P.

The bacterial tRNA processing enzyme ribonuclease P (RNase P) is a ribonucleoprotein composed of a approximately 400 nucleotide RNA and a smaller protein subunit. It has been established that RNase P RNA contacts the mature tRNA portion of pre-tRNA substrates, whereas RNase P protein interacts with the 5' leader sequence. However, specific interactions with substrate nucleotides flanking the cleavage site have not previously been defined.

Analysis of substrate recognition by the ribonucleoprotein endonuclease RNase P.

Ribonuclease P (RNase P), is a ribonucleoprotein complex that catalyzes the site-specific cleavage of pre-tRNA and a wide variety of other substrates. Although RNase P RNA is the catalytic subunit of the holoenzyme, the protein subunit plays a critical role in substrate binding. Thus, RNase P is an excellent model system for studying ribonucleoprotein function.

Evidence for a polynuclear metal ion binding site in the catalytic domain of ribonuclease P RNA.

Interactions with divalent metal ions are essential for the folding and function of the catalytic RNA component of the tRNA processing enzyme ribonuclease P (RNase P RNA). However, the number and location of specific metal ion interactions in this large, highly structured RNA are poorly understood. Using atomic mutagenesis and quantitative analysis of thiophilic metal ion rescue we provide evidence for metal ion interactions at the pro-R(P) and pro-S(P) non-bridging phosphate oxygens at nucleotide A67 in the universally conserved helix P4.

NAIM and site-specific functional group modification analysis of RNase P RNA: magnesium dependent structure within the conserved P1-P4 multihelix junction contributes to catalysis.

The tRNA processing endonuclease ribonuclease P contains an essential and highly conserved RNA molecule (RNase P RNA) that is the catalytic subunit of the enzyme. To identify and characterize functional groups involved in RNase P RNA catalysis, we applied self-cleaving ribozyme-substrate conjugates, on the basis of the RNase P RNA from Escherichia coli, in nucleotide analogue interference mapping (NAIM) and site-specific modification experiments. At high monovalent ion concentrations (3 M) that facilitate protein-independent substrate binding, we find that the ribozyme is largely insensitive to analogue substitution and that concentrations of Mg2+ (1.