Measuring multiple neurochemicals and related metabolites in blood and brain of the rhesus monkey by using dual microdialysis sampling and capillary hydrophilic interaction chromatography-mass spectrometry

In vivo measurement of multiple functionally related neurochemicals and metabolites (NMs) is highly interesting but remains challenging in the field of basic neuroscience and clinical research. We present here an analytical method for determining five functionally and metabolically related polar substances, including acetylcholine (quaternary ammonium), lactate and pyruvate (organic acids), as well as glutamine and glutamate (amino acids). These NMs are acquired from samples of the brain and the blood of non-human primates in parallel by dual microdialysis, and subsequently analyzed by a direct capillary hydrophilic interaction chromatography (HILIC)-mass spectrometry (MS) based method. To obtain high sensitivity in electrospray ionization (ESI)-MS, lactate and pyruvate were detected in negative ionization mode whereas the other NMs were detected in positive ionization mode during each HILIC-MS run. The method was validated for linearity, the limits of detection and quantification, precision, accuracy, stability and matrix effect. The detection limit of acetylcholine, lactate, pyruvate, glutamine, and glutamate was 150pM, 3μM, 2μM, 5nM, and 50nM, respectively. This allowed us to quantitatively and simultaneously measure the concentrations of all the substances from the acquired dialysates. The concentration ratios of both lactate/pyruvate and glutamine/glutamate were found to be higher in the brain compared to blood (p < 0.05). The reliable and simultaneous quantification of these five NMs from brain and blood samples allows us to investigate their relative distribution in the brain and blood, and most importantly paves the way for future non-invasive studies of the functional and metabolic relation of these substances to each other. Figure Measuring multiple polar multiple neurochemicals and related metabolites using HILIC-ESI/MS in combination with dual brain and blood samplin

Perpendicular magnetic anisotropy in conducting NiCo\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e4\u3c/sub\u3e films from spin-lattice coupling

High perpendicular magnetic anisotropy (PMA), a property needed for nanoscale spintronic applications, is rare in oxide conductors. We report the observation of a PMA up to 0.23 MJ/m3 in modestly strained (–0.3%) epitaxial NiCo2O4 films which are room-temperature ferrimagnetic conductors. Spin-lattice coupling manifested as magnetoelastic effect was found as the origin of the PMA. The in-plane x2-y2 states of Co on tetrahedral sites play crucial role in the magnetic anisotropy and spin-lattice coupling with an energy scale of 1 meV/f.u. The elucidation of the microscopic origin paves a way for engineering oxide conductors for PMA using metal/oxygen hybridizations

SHiFT: An Efficient, Flexible Search Engine for Transfer Learning

Transfer learning can be seen as a data- and compute-efficient alternative to training models from scratch. The emergence of rich model repositories, such as TensorFlow Hub, enables practitioners and researchers to unleash the potential of these models across a wide range of downstream tasks. As these repositories keep growing exponentially, efficiently selecting a good model for the task at hand becomes paramount. By carefully comparing various selection and search strategies, we realize that no single method outperforms the others, and hybrid or mixed strategies can be beneficial. Therefore, we propose SHiFT, the first downstream task-aware, flexible, and efficient model search engine for transfer learning. These properties are enabled by a custom query language SHiFT-QL together with a cost-based decision maker, which we empirically validate. Motivated by the iterative nature of machine learning development, we further support efficient incremental executions of our queries, which requires a careful implementation when jointly used with our optimizations

Naringenin prevents TGF-β1 secretion from breast cancer and suppresses pulmonary metastasis by inhibiting PKC activation

Presenting the incidence of pulmonary metastasis (mice with metastasis/total mice). Tumor-bearing mice treated with naringenin or 1D11 were imaged on day 24 using bags to avoid the bioluminescence from primary tumor. The mice with pulmonary metastases were numbered based on the bioluminescence signal. (TIF 26 kb

Separation and identification of mouse brain tissue microproteins using top‐down method with high resolution nanocapillary liquid chromatography mass spectrometry

Microproteins and endogenous peptides in the brain contain important substances that have critical roles in diverse biological processes, contributing to signal transduction and intercellular signaling. However, variability in their physical or chemical characteristics, such as molecule size, hydrophobicity, and charge states, complicate the simultaneous analysis of these compounds, although this would be highly beneficial for the field of neuroscience research. Here, we present a top-down analytical method for simultaneous analysis of microproteins and endogenous peptides using high- resolution nanocapillary LC-MS/MS. This method is detergent-free and digestion-free, which allows for extracting and preserving intact microproteins and peptides for direct LC-MS analysis. Both higher energy collision dissociation and electron-transfer dissociation fragmentations were used in the LC-MS analysis to increase the identification rate, and bioinformatics tools ProteinGoggle and PEAKS Studio software were utilized for database search. In total, we identified 471 microproteins containing 736 proteoforms, including brain-derived neurotrophic factor and a number of fibroblast growth factors. In addition, we identified 599 peptides containing 151 known or potential neuropeptides such as somatostatin-28 and neuropeptide Y. Our approach bridges the gap for the characterization of brain microproteins and peptides, which permits quantification of a diversity of signaling molecules for biomarker discovery or therapy diagnosis in the future