PubMed
A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice.
A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice.
Xenobiotica. 2018 Jun 13;:1-53
Authors: Wang YK, Yang XN, Liang WQ, Xiao Y, Zhao Q, Xiao XR, Gonzalez FJ, Li F
Abstract
1. To elucidate the metabolism of pazopanib, a metabolomics approach was performed based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole mass spectrometry. 2. A total of 22 pazopanib metabolites were identified in vitro and in vivo. Among these metabolites, 17 were novel, including several cysteine adducts and aldehyde derivatives. By screening using recombinant CYPs, CYP3A4 and CYP1A2 were found to be the main forms involved in the pazopanib hydroxylation. Formation of a cysteine conjugate (M3), an aldehyde derivative (M15) and two N-oxide metabolites (M18 and M20) from pazopanib could induce the oxidative stress that may be responsible in part for pazopanib-induced hepatotoxicity. 3. Morphological observation of the liver suggested that pazopanib (300 mg/kg) could cause liver injury. The aspartate transaminase and alanine aminotransferase in serum significantly increased after pazopanib (150, 300 mg/kg) treatment; this liver injury could be partially reversed by the broad-spectrum CYP inhibitor 1-aminobenzotriazole (ABT). Metabolomics analysis revealed that pazopanib could significantly change the levels of L-carnitine, proline and lysophosphatidylcholine 18:1 in liver. Additionally, drug metabolism-related gene expression analysis revealed that hepatic Cyp2d22 and Abcb1a (P-gp) mRNAs of were significantly lowered by pazopanib treatment. 4. In conclusion, this study provides a global view of pazopanib metabolism and clues to its influence on hepatic function.
PMID: 29897827 [PubMed - as supplied by publisher]
Cortisol, cortisone, and 4-methoxyphenylacetic acid as potential plasma biomarkers for early detection of non-small cell lung cancer.
Cortisol, cortisone, and 4-methoxyphenylacetic acid as potential plasma biomarkers for early detection of non-small cell lung cancer.
Int J Biol Markers. 2018 Jun 01;:1724600818778754
Authors: Xiang C, Jin S, Zhang J, Chen M, Xia Y, Shu Y, Guo R
Abstract
BACKGROUND: Lung cancer is the most common cause of cancer-related deaths in men and women worldwide. Novel diagnostic biomarkers are urgently required to enable the early detection and treatment of lung cancer, and using novel methods to explore tumor-related biomarkers is a hot topic in lung cancer research. The purpose of this study was to use ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) metabolomics analysis technology combined with multivariate data processing methods to identify potential plasma biomarkers for non-small cell lung cancer (NSCLC).
METHODS: Plasma samples from 99 NSCLC patients and 112 healthy controls were randomly divided into the screening group and the validation group, respectively. UPLC-MS metabolomics analysis technology combined with multivariate data processing methods were used to identify potential plasma biomarkers for NSCLC.
RESULTS: A total of 254 metabolites were detected and validated in plasma. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) modeling indicated that 28 endogenous metabolites were present at significantly different levels in patients with NSCLC than healthy controls (variable importance in projection (VIP)>1 and P<0.001 (independent samples t-test) in both the screening group and the validation group). Further analysis revealed that cortisol, cortisone, and 4-methoxyphenylacetic acid had high sensitivity and specificity values as biomarkers for discriminating between NSCLC and healthy controls. Significant associations between specific plasma metabolites and the pathological type or stage of NSCLC were also observed.
CONCLUSIONS: Metabolomics has the potential to distinguish between NSCLC patients and healthy controls, and may reveal new plasma biomarkers for the early detection of NSCLC.
PMID: 29896992 [PubMed - as supplied by publisher]
Omics in Zebrafish Teratogenesis.
Related Articles
Omics in Zebrafish Teratogenesis.
Methods Mol Biol. 2018;1797:421-441
Authors: Piña B, Navarro L, Barata C, Raldúa D, Martínez R, Casado M
Abstract
The genome revolution represents a complete change on our view of biological systems. The quantitative determination of changes in all major molecular components of the living cells, the "omics" approach, opened whole new fields for all health sciences. Genomics, transcriptomics, proteomics, metabolomics, and others, together with appropriate prediction and modeling tools, will mark the future of developmental toxicity assessment both for wildlife and humans. This is especially true for disciplines, like teratology, which rely on studies in model organisms, as studies at lower levels of organization are difficult to implement. Rodents and frogs have been the favorite models for studying human reproductive and developmental disorders for decades. Recently, the study of the development of zebrafish embryos (ZE) is becoming a major alternative tool to adult animal testing. ZE intrinsic characteristics makes this model a unique system to analyze in vivo developmental alterations that only can be studied applying in toto approaches. Moreover, under actual legislations, ZE is considered as a replacement model (and therefore, excluded from animal welfare regulations) during the first 5 days after fertilization. Here we review the most important components of the zebrafish toolbox available for analyzing early stages of embryotoxic events that could eventually lead to teratogenesis.
PMID: 29896707 [PubMed - in process]
Exploratory lipidomics in patients with nascent Metabolic Syndrome.
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Exploratory lipidomics in patients with nascent Metabolic Syndrome.
J Diabetes Complications. 2018 May 25;:
Authors: Ramakrishanan N, Denna T, Devaraj S, Adams-Huet B, Jialal I
Abstract
BACKGROUND: Metabolic Syndrome (MetS) is a cardio-metabolic cluster that confers an increased risk of developing both diabetes and atherosclerotic cardiovascular disease (ASCVD). The mechanisms governing the increased ASCVD risk remains to be elucidated. Moreover, lipidomics poses as an exciting new tool that has potential to shed more light on the pathogenesis of MetS.
OBJECTIVE: The aim of this study was to explore the lipidome in an unbiased fashion in patients with nascent MetS uncomplicated by diabetes and CVD.
METHODS: Patients with nascent MetS (n = 30) without diabetes or ASCVD and controls (n = 20) who participated in the study had normal hepatic and renal function. Early morning urine samples from patients were collected and frozen at -70° until analysis. Lipidomic analyses were undertaken at the National Institute of Health Western Metabolomics Center.
RESULTS: Phosphatidylcholine 34:2, PC (34:2) was significantly increased in patients with MetS compared to controls. PC (34:2) had a significant positive correlation with waist circumference, plasma glucose, free fatty acid, and triglyceride levels. It had a significant positive correlation with pro-inflammatory markers such as plasma hs CRP, IL-1b, and IL-8. Additionally, PC (34:2) significantly correlated positively with Leptin and inversely with adiponectin. Levels of various acyl carnitines and PC34:1 were not significantly altered.
CONCLUSION: We propose that PC (34:2) could emerge as a novel biomarker in MetS that promotes a pro-inflammatory state.
PMID: 29895440 [PubMed - as supplied by publisher]
Non-targeted investigation of benthic invertebrates (Chironomus riparius) exposed to wastewater treatment plant effluents using nanoliquid chromatography coupled to high-resolution mass spectrometry.
Related Articles
Non-targeted investigation of benthic invertebrates (Chironomus riparius) exposed to wastewater treatment plant effluents using nanoliquid chromatography coupled to high-resolution mass spectrometry.
Chemosphere. 2018 Apr;196:347-353
Authors: Berlioz-Barbier A, Buleté A, Fildier A, Garric J, Vulliet E
Abstract
Nanoliquid chromatography (nanoLC) was coupled to high-resolution mass spectrometry (HRMS) to perform a non-targeted investigation on benthic invertebrates, Chironomus riparius exposed to wastewater treatment plant (WWTP) effluents. Insect larvae represent a complex and low-weight matrix that required the use of a miniaturized Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method of extraction followed by nanoLC-HRMS to perform the analysis. The optimization of this coupling in terms of separation conditions including trapping step, detection conditions and data treatment provided reproducible fingerprints on insect larvae exposed to WWTP effluents with both in situ and ex-situ approaches. Statistical treatments such as principal component analysis highlighted the impact of WWTP effluents on the metabolome of insect larvae and showed the influence of exposure conditions. The identification of discriminating signals (m/z, tR) matched with several potential endogenous biomarkers. These are mainly fatty acids, indicating a change in lipid metabolism that can be correlated with exposure to WWTP effluents. Several xenobiotics have also been detected, including ibuprofen and propranolol, whose identities have been confirmed by analytical standards. This work demonstrates the effectiveness and sensitivity of nanoLC-HRMS based environmental non-targeted approaches in ecotoxicological studies and provides the first profiling data for a very small aquatic invertebrate.
PMID: 29310071 [PubMed - indexed for MEDLINE]
Bioenergetics of Monoterpenoid Essential Oil Biosynthesis in Nonphotosynthetic Glandular Trichomes.
Related Articles
Bioenergetics of Monoterpenoid Essential Oil Biosynthesis in Nonphotosynthetic Glandular Trichomes.
Plant Physiol. 2017 Oct;175(2):681-695
Authors: Johnson SR, Lange I, Srividya N, Lange BM
Abstract
The commercially important essential oils of peppermint (Mentha × piperita) and its relatives in the mint family (Lamiaceae) are accumulated in specialized anatomical structures called glandular trichomes (GTs). A genome-scale stoichiometric model of secretory phase metabolism in peppermint GTs was constructed based on current biochemical and physiological knowledge. Fluxes through the network were predicted based on metabolomic and transcriptomic data. Using simulated reaction deletions, this model predicted that two processes, the regeneration of ATP and ferredoxin (in its reduced form), exert substantial control over flux toward monoterpenes. Follow-up biochemical assays with isolated GTs indicated that oxidative phosphorylation and ethanolic fermentation were active and that cooperation to provide ATP depended on the concentration of the carbon source. We also report that GTs with high flux toward monoterpenes express, at very high levels, genes coding for a unique pair of ferredoxin and ferredoxin-NADP+ reductase isoforms. This study provides, to our knowledge, the first evidence of how bioenergetic processes determine flux through monoterpene biosynthesis in GTs.
PMID: 28838953 [PubMed - indexed for MEDLINE]
Cell-Fate Specification in Arabidopsis Roots Requires Coordinative Action of Lineage Instruction and Positional Reprogramming.
Related Articles
Cell-Fate Specification in Arabidopsis Roots Requires Coordinative Action of Lineage Instruction and Positional Reprogramming.
Plant Physiol. 2017 Oct;175(2):816-827
Authors: Yu Q, Li P, Liang N, Wang H, Xu M, Wu S
Abstract
Tissue organization and pattern formation within a multicellular organism rely on coordinated cell division and cell-fate determination. In animals, cell fates are mainly determined by a cell lineage-dependent mechanism, whereas in plants, positional information is thought to be the primary determinant of cell fates. However, our understanding of cell-fate regulation in plants mostly relies on the histological and anatomical studies on Arabidopsis (Arabidopsis thaliana) roots, which contain a single layer of each cell type in nonvascular tissues. Here, we investigate the dynamic cell-fate acquisition in modified Arabidopsis roots with additional cell layers that are artificially generated by the misexpression of SHORT-ROOT (SHR). We found that cell-fate determination in Arabidopsis roots is a dimorphic cascade with lineage inheritance dominant in the early stage of pattern formation. The inherited cell identity can subsequently be removed or modified by positional information. The instruction of cell-fate conversion is not a fast readout during root development. The final identity of a cell type is determined by the synergistic contribution from multiple layers of regulation, including symplastic communication across tissues. Our findings underline the collaborative inputs during cell-fate instruction.
PMID: 28821591 [PubMed - indexed for MEDLINE]
metabolomics; +17 new citations
17 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2018/06/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.
metabolomics; +17 new citations
17 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2018/06/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.
metabolomics; +17 new citations
17 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2018/06/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.
metabolomics; +17 new citations
17 new pubmed citations were retrieved for your search.
Click on the search hyperlink below to display the complete search results:
metabolomics
These pubmed results were generated on 2018/06/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books.
Citations may include links to full-text content from PubMed Central and publisher web sites.
Quantitative Metabolomics in Alzheimer's Disease: Technical Considerations for Improved Reproducibility.
Quantitative Metabolomics in Alzheimer's Disease: Technical Considerations for Improved Reproducibility.
Methods Mol Biol. 2018;1779:463-470
Authors: Veiga S, Wahrheit J, Rodríguez-Martín A, Sonntag D
Abstract
Metabolomics is the comprehensive analysis of small molecules (metabolites) that are intermediates or endpoints of metabolism. Since metabolites change more rapidly to both external and internal stimuli than genes and proteins, metabolomics provides a more sensitive tool to study physiological changes to a wide range of factors such age, medication, or disease status. Therefore, metabolomics is being increasingly used for the study of several pathological states, including complex diseases like Alzheimer's disease (AD).Both untargeted and targeted metabolomics have been applied for AD and both have provided diagnostic algorithms that accurately discriminate healthy patients from patients with AD by combining different metabolites. However, none of these algorithms have been replicated in larger, different cohorts, and a consensus in methodology has been claimed by the scientific community. The AbsoluteIDQ® p180 Kit (Biocrates, Life Science AG, Innsbruck, Austria) is to date the only commercially available, validated, and standardized assay that measures up to 188 metabolites in biological samples. This kit unifies methodology in a common user manual and provides quantitative measurements of metabolites, thus facilitating an easier comparison among studies and reducing the technical variability that might contribute to replication failures. Nevertheless, recent studies showed no replication even when using this kit, suggesting that additional measures should be taken to achieve replication of metabolite-based discriminative algorithms. The aim of this chapter is to provide technical guidance on how to apply quantitative metabolomic data to the definition of discriminative algorithms for the diagnosis of neurodegenerative diseases such as AD. This chapter will provide an overview of technical aspects on the whole process, from blood sampling to raw data handling, and will highlight several technical aspects in the process that could hamper replication attempts even when using validated and standardized assays, such as the AbsoluteIDQ® p180 Kit.
PMID: 29886550 [PubMed - in process]
TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel.
TKTL1 modulates the response of paclitaxel-resistant human ovarian cancer cells to paclitaxel.
Biochem Biophys Res Commun. 2018 Jun 07;:
Authors: Zheng X, Li H
Abstract
Transketolase-like 1 (TKTL1) plays an important role in the pentose phosphate pathway (PPP) branch. The main obstacle of ovarian cancer treatment is chemotherapeutic resistance. We investigated whether inhibiting TKTL1 in OC3/TAX300 cells could re-sensitize paclitaxel-resistant cells to paclitaxel and proposed a mechanism of action. Western blotting revealed that TKTL1 expression levels in OC3/Tax300 cells were significantly higher than those in OC3 cells. Inhibition of TKTL1 significantly decreased the cellular proliferation rate and IC50 for paclitaxel. Metabolomics revealed that NADPH levels were reduced in the si-TKTL1 group, whereas NADP+ was increased compared with the level in the negative si-TKTL1 group. A 2.2-fold increase in the ROS level and an obvious increase in the cell apoptosis rate were observed in the si-TKTL1+paclitaxel group compared with those in the negative si-TKTL1+paclitaxel and OC3/Tax300 + paclitaxel groups. Western blotting revealed that Bax and Caspase 3 proteins were up-regulated, whereas Bcl-2 expression was down-regulated. Quantitative RT-PCR revealed no changes in gst-π or mrp1 gene expression in the three groups, whereas GSH levels were reduced in the si-TKTL1 group as verified by metabolomics. TKTL1 inhibition also reduced tumor growth in vivo. Collectively, TKTL1 down-regulation sensitized paclitaxel-resistant OC3/Tax300 ovarian cancer cells to paclitaxel.
PMID: 29885837 [PubMed - as supplied by publisher]
Metabolomics and cytotoxicity of monomethylhydrazine (MMH) and (E)-1,1,4,4-tetramethyl-2-tetrazene (TMTZ), two liquid propellants.
Related Articles
Metabolomics and cytotoxicity of monomethylhydrazine (MMH) and (E)-1,1,4,4-tetramethyl-2-tetrazene (TMTZ), two liquid propellants.
Toxicol In Vitro. 2018 Jun 06;:
Authors: Guyot L, Machon C, Honorat M, Manship B, Bouard C, Vigneron A, Puisieux A, Labarthe E, Jacob G, Dhenain A, Guitton J, Payen L
Abstract
Hydrazine-based liquid propellants are routinely used for space rocket propulsion, in particular monomethylhydrazine (MMH), although such compounds are highly hazardous. For several years, great efforts were devoted to developing a less hazardous molecule. To explore the toxicological effects of an alternative compound, namely (E)-1,1,4,4-tetramethyl-2-tetrazene (TMTZ), we exposed various cellular animal and human models to this compound and to the reference compound MMH. We observed no cytotoxic effects following exposure to TMTZ in animal, as well as human models. However, although the three animal models were unaffected by MMH, exposure of the human hepatic HepaRG cell model revealed that apoptotic cytotoxic effects were only detectable in proliferative human hepatic HepaRG cells and not in differentiated cells, although major biochemical modifications were uncovered in the latter. The present findings indicate that the metabolic mechanisms of MMH toxicity is close to those described for hydrazine with numerous biochemical alterations induced by mitochondrial disruption, production of radical species, and aminotransferase inhibition. The alternative TMTZ molecule had little impact on cellular viability and proliferation of rodent and human dermic and hepatic cell models. TMTZ did not produce any metabolomic effects and appears to be a promising putative industrial alternative to MMH.
PMID: 29885439 [PubMed - as supplied by publisher]
New Frontiers of Metallomics: Elemental and Species-Specific Analysis and Imaging of Single Cells.
Related Articles
New Frontiers of Metallomics: Elemental and Species-Specific Analysis and Imaging of Single Cells.
Adv Exp Med Biol. 2018;1055:245-270
Authors: Jiménez-Lamana J, Szpunar J, Łobinski R
Abstract
Single cells represent the basic building units of life, and thus their study is one the most important areas of research. However, classical analysis of biological cells eludes the investigation of cell-to-cell differences to obtain information about the intracellular distribution since it only provides information by averaging over a huge number of cells. For this reason, chemical analysis of single cells is an expanding area of research nowadays. In this context, metallomics research is going down to the single-cell level, where high-resolution high-sensitive analytical techniques are required. In this chapter, we present the latest developments and applications in the fields of single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS), mass cytometry, laser ablation (LA)-ICP-MS, nanoscale secondary ion mass spectrometry (nanoSIMS), and synchrotron X-ray fluorescence microscopy (SXRF) for single-cell analysis. Moreover, the capabilities and limitations of the current analytical techniques to unravel single-cell metabolomics as well as future perspectives in this field will be discussed.
PMID: 29884968 [PubMed - in process]
Advanced Nuclear and Related Techniques for Metallomics and Nanometallomics.
Related Articles
Advanced Nuclear and Related Techniques for Metallomics and Nanometallomics.
Adv Exp Med Biol. 2018;1055:213-243
Authors: Li YF, Zhao J, Gao Y, Chen C, Chai Z
Abstract
Metallomics, focusing on the global and systematic understanding of the metal uptake, trafficking, role, and excretion in biological systems, has attracted more and more attention. Metal-related nanomaterials, including metallic and metal-containing nanomaterials, have unique properties compared to their macroscale counterparts and therefore require special attention. The absorption, distribution, metabolism, excretion (ADME) behavior of metal-related nanomaterials in the biological systems is influenced by their physicochemical properties, the exposure route, and the microenvironment of the deposition site. Nanomaterials not only may interact directly or indirectly with genes, proteins, and other molecules to bring genotoxicity, immunotoxicity, DNA damage, and cytotoxicity but may also stimulate the immune responses, circumvent tumor resistance, and inhibit tumor metastasis. Because of their advantages of absolute quantification, high sensitivity, excellent accuracy and precision, low matrix effects, and nondestructiveness, nuclear and related analytical techniques have been playing important roles in the study of metallomics and nanometallomics. In this chapter, we present a comprehensive overview of nuclear and related analytical techniques applied to the quantification of metallome and nanometallome, the biodistribution, bioaccumulation, and transformation of metallome and nanometallome in vivo, and the structural analysis. Besides, metallomics and nanometallomics need to cooperate with other -omics, like genomics, proteomics, and metabolomics, to obtain the knowledge of underlying mechanisms and therefore to improve the application performance and to reduce the potential risk of metallome and nanometallome.
PMID: 29884967 [PubMed - in process]
Environmental Metallomics.
Related Articles
Environmental Metallomics.
Adv Exp Med Biol. 2018;1055:39-66
Authors: Rodríguez-Moro G, Ramírez-Acosta S, Arias-Borrego A, García-Barrera T, Gómez-Ariza JL
Abstract
Metallomics is the new paradigm about the metallobiomolecules related to living organisms, considering the interactions between toxic and essential metals, transport through biological fluids, passing across biological membranes and interfaces, synergic and antagonist actions among metal species, and alterations in metabolic pathways triggered by overexpression or inhibition of these metallobiomolecules. These challenging studies require the development of new analytical approaches in order to get suitable information of these species close to their native environment which has promoted the application of new tools based in mass spectrometry under the double focus of elemental (ICP-MS) and molecular (Qq-TOF-MS) mass spectrometry, generally arranged with chromatography in multidimensional platforms. The driving force for the design of these new analytical instrumental arrangements is the analyst imagination who adapts the new metallomic methodology to the new problems. In this work the most recent metallomic approaches proposed have been considered, deepening their application to the most frequent problems related to metal toxicity in environmental issues, such as exposure experiments of mice to toxic metals, interactions and homeostasis of metals, metal imaging, metabolic alterations caused by metallobiomolecules over- or down-expressed, and more interestingly real-life consequences of metal species expression in environmental field studies. In this way, the application of two-dimensional chromatographic approaches with ICP-MS detection, the use of multidimensional chromatography-column-switching-ICP-MS devices, metal imaging with LA-ICP-MS, combined application of metallomics and metabolomics for environmental toxicological appraisal, and the application of these metallomic techniques in environmental field studies have been reviewed.
PMID: 29884961 [PubMed - in process]
Effects of mobile phone exposure on metabolomics in the male and female reproductive systems.
Related Articles
Effects of mobile phone exposure on metabolomics in the male and female reproductive systems.
Environ Res. 2018 May 16;:
Authors: Altun G, Deniz ÖG, Yurt KK, Davis D, Kaplan S
Abstract
With current advances in technology, a number of epidemiological and experimental studies have reported a broad range of adverse effects of electromagnetic fields (EMF) on human health. Multiple cellular mechanisms have been proposed as direct causes or contributors to these biological effects. EMF-induced alterations in cellular levels can activate voltage-gated calcium channels and lead to the formation of free radicals, protein misfolding and DNA damage. Because rapidly dividing germ cells go through meiosis and mitosis, they are more sensitive to EMF in contrast to other slower-growing cell types. In this review, possible mechanistic pathways of the effects of EMF exposure on fertilization, oogenesis and spermatogenesis are discussed. In addition, the present review also evaluates metabolomic effects of GSM-modulated EMFs on the male and female reproductive systems in recent human and animal studies. In this context, experimental and epidemiological studies which examine the impact of mobile phone radiation on the processes of oogenesis and spermatogenesis are examined in line with current approaches.
PMID: 29884548 [PubMed - as supplied by publisher]
Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.
Related Articles
Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.
Immunity. 2018 May 25;:
Authors: Tsui C, Martinez-Martin N, Gaya M, Maldonado P, Llorian M, Legrave NM, Rossi M, MacRae JI, Cameron AJ, Parker PJ, Leitges M, Bruckbauer A, Batista FD
Abstract
PKCβ-null (Prkcb-/-) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral infection. At the cellular level, we have shown that Prkcb-/- B cells exhibited defective antigen polarization and mTORC1 signaling. While altered antigen polarization impaired antigen presentation and likely restricted the potential of GC development, defective mTORC1 signaling impaired metabolic reprogramming, mitochondrial remodeling, and heme biosynthesis in these cells, which altogether overwhelmingly opposed plasma cell differentiation. Taken together, our study reveals mechanistic insights into the function of PKCβ as a key regulator of B cell polarity and metabolic reprogramming that instructs B cell fate.
PMID: 29884460 [PubMed - as supplied by publisher]
Characteristic features of the unique house sake yeast strain Saccharomyces cerevisiae Km67 used for industrial sake brewing.
Related Articles
Characteristic features of the unique house sake yeast strain Saccharomyces cerevisiae Km67 used for industrial sake brewing.
J Biosci Bioeng. 2018 Jun 05;:
Authors: Takao Y, Takahashi T, Yamada T, Goshima T, Isogai A, Sueno K, Fujii T, Akao T
Abstract
For several decades, almost all sake has been brewed with sake yeast Saccharomyces cerevisiae Kyokai no. 7 (K7) group strains. Although the widespread use of these strains has contributed to sake quality improvement, it may have lessened the diversity of sake gustatory properties brought about by house sake yeast (indigenous yeast of sake brewery). Sake yeast S. cerevisiae strain Km67 derives from the house yeast strain of Kiku-masamune Sake Brewing Co., Ltd., and it has been playing a central role in industrial sake brewing for decades. By using DNA sequencing, we revealed that strain Km67 does not possess specific loss-of-function mutations of stress response-related genes, which are characteristic of K7 group strains. Km67 had higher stress tolerance than K7 group strains likely because of the more efficient function of the stress response and heat shock elements in this strain. Sensory evaluation and taste sensor analysis demonstrated that sake brewed with Km67 had characteristically thicker body than sake brewed with K7 group strains. Chemical analysis suggested that unique sensory properties of the sake brewed with Km67 were due to high citramalic acid concentration. Taken together, these results revealed that strain Km67 differs from K7 group strains by genetic background and confers unique chemical composition and taste qualities upon sake it generates. It is expected that sake quality and gustatory properties will be diversified by utilizing house yeast such as strain Km67.
PMID: 29884321 [PubMed - as supplied by publisher]