Site-Specific Clustering of Bioactive Signaling Molecules Predicted In Situ by Space and Time Coherent Mapping for Imaging Mass Spectrometry.

Anatomical representation of site-specific clustering of biomolecules is a powerful way of predicting a potential interaction among signaling cascades and orchestrating molecular functions in cells and organs. The greater the number of molecules visualized simultaneously, the deeper we can understand each molecule's role in cellular metabolism and function. In the present study, we investigated site-specific localization of small biomolecules in the slug using Space and Time Coherent Mapping (STCM), a key technology in matrix-assisted laser desorption ionization time-of-flight imaging mass spectrometry.

Understanding Cellular, Molecular, and Functional Specificity, Heterogeneity, and Diversity of the Endocannabinoid System.

The endocannabinoid system (ECS) is a widely recognized lipid messenger system involved in many aspects of our health and diseases [...

Pillar Array Mixer for Postcolumn Derivatization Integrated into Liquid Chromatography-Based Microfluidic Device.

The chemical derivatization of target analytes can enhance the sensitivity and selectivity of separation-based methods for metabolite analysis using microfluidic devices. However, the development of chromatography-based microfluidic devices with integrated derivatization units is challenging. In this study, a novel derivatization unit with a pillar array (PA)-based mixing channel was developed for postcolumn derivatization during on-chip liquid chromatography (LC).

Visualization of Anorectal Lymphatic Flow Using Indocyanine Green Fluorescence Imaging: An Observational Study.

Background/aim: Currently, only a small part of functional lymphatic flow around the anorectal region has been anatomically analyzed. Despite the fact that local recurrence is often experienced in the pelvic floor, the functional lymphatic network in this region has rarely been studied due to difficulties in observation. This prospective observational study aimed to observe anorectal lymphatic flow around the pelvic floor using intraoperative indocyanine green fluorescence imaging during laparoscopic or robot-assisted rectal surgery.

Large-Scale Multi-Omic Approaches and Atlas-Based Profiling for Cellular, Molecular, and Functional Specificity, Heterogeneity, and Diversity in the Endocannabinoid System.

The endocannabinoid system (ECS) is a widely-recognized lipid messenger system involved in many aspects of our our lives in health and diseases [...

AJICAP Second Generation: Improved Chemical Site-Specific Conjugation Technology for Antibody-Drug Conjugate Production.

The site-directed chemical conjugation of antibodies remains an area of great interest and active efforts within the antibody-drug conjugate (ADC) community. We previously reported a unique site modification using a class of immunoglobulin-G (IgG) Fc-affinity reagents to establish a versatile, streamlined, and site-selective conjugation of native antibodies to enhance the therapeutic index of the resultant ADCs. This methodology, termed "AJICAP", successfully modified Lys248 of native antibodies to produce site-specific ADC with a wider therapeutic index than the Food and Drug Administration-approved ADC, Kadcyla.

Space and Time Coherent Mapping for Subcellular Resolution of Imaging Mass Spectrometry.

Space and time coherent mapping (STCM) is a technology developed in our laboratory for improved matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) imaging mass spectrometry (IMS). STCM excels in high spatial resolutions, which probe-based scanning methods cannot attain in conventional MALDI IMS. By replacing a scanning probe with a large field laser beam, focusing ion optics, and position-sensitive detectors, STCM tracks the entire flight trajectories of individual ions throughout the ionization process and visualizes the ionization site on the sample surface with a subcellular scale of precision and a substantially short acquisition time.

Comparison of Short-term Outcomes of a Self-expandable Metallic Stent as a Bridge to Laparoscopic Surgery between Right- and Left-sided Obstructive Colorectal Cancers: A Retrospective Observational Study.

Objectives: Few studies have compared the tumor-site-based postoperative short-term outcomes of a bridge to surgery using self-expandable metallic stents. This study compared the perioperative outcomes following stent placement between right- and left-sided obstructive colorectal cancers, focusing on patients undergoing laparoscopic surgery.

Methods: This study included 127 patients with stage I-IV obstructive colorectal cancer (right-sided, n = 25 [19.

Postoperative colon perforation due to the tip of the transanal decompression tube after laparoscopic low anterior resection: A case report.

A 66-year-old man underwent laparoscopic low anterior resection for rectal cancer. A transanal decompression tube (24Fr Nelaton catheter) was placed laparoscopically during the surgery. Contrast enema on postoperative day 5 showed perforation of the sigmoid colon around the tip of the tube, and emergency laparotomy was performed.

Ghrelin-O-acyltransferase (GOAT) acylates ghrelin in the hippocampus.

Ghrelin is an appetite-stimulating peptide hormone and produced in the stomach. Serine 3 on ghrelin must be acylated by the lipid transferase known as Ghrelin-O-acyltransferase (GOAT) in order for the peptide to become physiologically-active and bind to the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). GHSR1a has been known to be expressed in the feeding center of the hypothalamus.

Neurodegenerative processes accelerated by protein malnutrition and decelerated by essential amino acids in a tauopathy mouse model.

Protein malnutrition is epidemiologically suggested as a potential risk factor for senile dementia, although molecular mechanisms linking dietary proteins and amino acids to neurodegeneration remain unknown. Here, we show that a low-protein diet resulted in down-regulated expression of synaptic components and a modest acceleration of brain atrophy in mice modeling neurodegenerative tauopathies. Notably, these abnormal phenotypes were robustly rescued by the administration of seven selected essential amino acids.

Intake of Seven Essential Amino Acids Improves Cognitive Function and Psychological and Social Function in Middle-Aged and Older Adults: A Double-Blind, Randomized, Placebo-Controlled Trial.

To delay the onset of dementia, it is important for healthy adults to take preventive actions before the cognitive function clearly declines. Protein malnutrition is a potential risk factor for senile dementia, although the precise link between protein/amino acid nutrition and cognitive function is unknown. The purpose of this study was to examine the effect of the ingestion of seven selected essential amino acids as a granular powder, namely, leucine, phenylalanine, and lysine supplemented with isoleucine, histidine, valine, and tryptophan on cognitive and psychosocial functions in healthy adults.

Protein Deficiency-Induced Behavioral Abnormalities and Neurotransmitter Loss in Aged Mice Are Ameliorated by Essential Amino Acids.

Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with memory function, and elderly people with high protein intake have a low risk of mild cognitive impairment. Although the beneficial roles of protein nutrition in maintaining brain function in aged people are well demonstrated, little is known about the mechanism by which dietary intake of protein affects memory and brain conditions.

Reduced chain length in myelin sphingolipids and poorer motor coordination in mice deficient in the fatty acid elongase .

Very-long-chain fatty acids, with a chain length of >C20, are abundant in myelin sphingolipids. Recently, a de novo mutation in the gene, which encodes fatty acid elongase, was identified in patients with neurocutaneous disorders involving skin ichthyosis and multiple neurological abnormalities, including hypomyelination, spastic paraplegia, and high-frequency deafness. However, the consequences of deficiency for lipid composition and detailed pathological changes in the brain remain unclear.

Optimization of tris(2-carboxyethyl) phosphine reduction conditions for fast analysis of total biothiols in mouse serum samples.

In this study, we investigated suitable conditions for the reduction of disulfides in mouse serum samples by tris(2-carboxyethyl) phosphine (TCEP) for fast analysis of total biothiols. Disulfides were reduced with TCEP, and then, thiols were derivatized with the fluorogenic reagent, ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F). Interference peaks on chromatograms of mouse serum samples disappeared when the TCEP reaction was conducted on ice instead of at room temperature, which is used classically.

Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism.

Ghrelin upregulates the phosphorylation of the GluN2B subunit of the NMDA receptor by activating GHSR1a and Fyn in the rat hippocampus.

Ghrelin and its receptor GHSR1a have been shown to exert numerous physiological functions in the brain, in addition to the well-established orexigenic role in the hypothalamus. Earlier work indicated that ghrelin stimulated the phosphorylation of the GluN1 subunit of the NMDA receptor (NMDAR) and enhanced synaptic transmission in the hippocampus. In the present study, we report that the exogenous application of ghrelin increased GluN2B phosphorylation.

Liquid Chromatography Chip with Low-Dispersion and Low-Pressure-Drop Turn Structure Utilizing a Distribution-Controlled Pillar Array.

To realize efficient, fast separations on pillar array columns with turns, a novel turn with low-dispersion and low-pressure-drop properties was developed. This "pillar-distribution-controlled" (PDC) turn was designed as a constant-radius turn filled with octagonal pillars that were arranged to control the linear velocity of the mobile phase in the radial direction. After the pillar positions were adjusted by computational fluid dynamics analysis, 27 mm long pillar array columns with two turns were fabricated on a 20 × 20 mm(2) silicon glass plate.

Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity.

GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca(2+)]i) and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores.

Determination and characterization of total thiols in mouse serum samples using hydrophilic interaction liquid chromatography with fluorescence detection and mass spectrometry.

Biothiols such as homocysteine, cysteine, and glutathione play many biologically important roles, especially in reduction-oxidation homeostasis and resistance to oxidative stress, and the measurement of their concentrations in model animal fluids is important in clarifying the pathology of thiol-related diseases. In this study, an analytical method for total biothiols in mouse serum using hydrophilic interaction liquid chromatography (HILIC) with fluorescence detection was developed. Mouse serum samples were derivatized with ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F), after reduction by tris(2-carboxyethyl)phosphine.

Ghrelin receptor activity amplifies hippocampal N-methyl-d-aspartate receptor-mediated postsynaptic currents and increases phosphorylation of the GluN1 subunit at Ser896 and Ser897.

Although ghrelin and its cognate receptor growth hormone secretagogue receptor (GHSR1a) are highly localized in the hypothalamic nuclei for the regulation of metabolic states and feeding, GHSR1a is also highly localized in the hippocampus, suggesting its involvement in extra-hypothalamic functions. Indeed, exogenous application of ghrelin has been reported to improve hippocampal learning and memory. However, the underlying mechanism of ghrelin regulation of hippocampal functions is poorly understood.

Development of analytical method for catechol compounds in mouse urine using hydrophilic interaction liquid chromatography with fluorescence detection.

An analytical method for catecholamines and related compounds using hydrophilic interaction liquid chromatography (HILIC) with native fluorescence detection has been developed. We found that ZIC-cHILIC with phosphorylcholine was suitable for the separation of catechol compounds with good peak shapes among six different HILIC columns (Inertsil SIL, Inertsil Amide, Inertsil Diol, TSKgel NH2-100, ZIC-HILIC, and ZIC-cHILIC). Using ZIC-cHILIC, eight catechol compounds (dopamine, epinephrine, norepinephrine, 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylglycol, 3,4-dihydroxymandelic acid, and internal standard 3,4-dihydroxybenzylamine) were separated within 15min.

Recent advances in hydrophilic interaction chromatography for quantitative analysis of endogenous and pharmaceutical compounds in plasma samples.

There is an increasing need for new analytical methods that can handle a large number of analytes in complex matrices. Hydrophilic interaction chromatography (HILIC) has recently been demonstrated as an important supplement to reversed-phase liquid chromatography for polar analytes, particularly endogenous compounds. With the increasing popularity of HILIC, progressively more polar phases with diverse functional groups have been developed.

Analytical methods involving separation techniques for determination of low-molecular-weight biothiols in human plasma and blood.

Low-molecular-weight biothiols such as homocysteine, cysteine, and glutathione are metabolites of the sulfur cycle and play important roles in biological processes such as the antioxidant defense network, methionine cycle, and protein synthesis. Thiol concentrations in human plasma and blood are related to diseases such as cardiovascular disease, neurodegenerative disease, and cancer. The concentrations of homocysteine, cysteine, and glutathione in plasma samples from healthy human subjects are approximately in the range of 5-15, 200-300, and 1-5 μM, respectively.