In vivo manipulation of human gut Bacteroides fitness by abiotic oligosaccharides.

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet.

Lipidomic analysis of Porphyromonas gingivalis reveals novel glycerol bisphosphoceramide, phosphatidyl-, and phosphoglycerol dipeptide lipid families.

Porphyromonas gingivalis, like other members of the phylum Bacteroidetes (synonym Bacteroidota), synthesizes several classes of dihydroceramides and peptidolipids. Using a similar strategy as that recently used to delimit the lipidome of its close relative Bacteroides fragilis, we applied linear ion trap multiple-stage mass spectrometry (linear ion trap MS) with high-resolution mass spectrometry, to structurally characterize the complete lipidome of P. gingivalis and compare it to B.

The sphingolipids ceramide and inositol phosphorylceramide protect the Leishmania major membrane from sterol-specific toxins.

The accessibility of sterols in mammalian cells to exogenous sterol-binding agents has been well-described previously, but sterol accessibility in distantly related protozoa is unclear. The human pathogen Leishmania major uses sterols and sphingolipids distinct from those used in mammals. Sterols in mammalian cells can be sheltered from sterol-binding agents by membrane components, including sphingolipids, but the surface exposure of ergosterol in Leishmania remains unknown.

Lipidome of the Genus Containing New Peptidolipid and Sphingolipid Families Revealed by Multiple-Stage Mass Spectrometry.

The anaerobic bacteria of the group including , , and in genus are among the most commonly found human gut microbiota. They are generally commensal but are also opportunistic pathogens. Both the inner and outer membranes of the cell envelope contain abundant lipids with diversified structures, and dissection of the lipid composition of the inner and outer membrane fractions is important for understanding the biogenesis of this multilaminate wall structure.

Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1.

Tandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE).

Expression of malic enzyme reveals subcellular carbon partitioning for storage reserve production in soybeans.

Central metabolism produces amino and fatty acids for protein and lipids that establish seed value. Biosynthesis of storage reserves occurs in multiple organelles that exchange central intermediates including two essential metabolites, malate, and pyruvate that are linked by malic enzyme. Malic enzyme can be active in multiple subcellular compartments, partitioning carbon and reducing equivalents for anabolic and catabolic requirements.

Sex differences in brain tumor glutamine metabolism reveal sex-specific vulnerabilities to treatment.

Background: Brain cancer incidence and mortality rates are greater in males. Understanding the molecular mechanisms that underlie those sex differences could improve treatment strategies. Although sex differences in normal metabolism are well described, it is currently unknown whether they persist in cancerous tissue.

Oncogenic Gq/11 signaling acutely drives and chronically sustains metabolic reprogramming in uveal melanoma.

Metabolic reprogramming has been shown to occur in uveal melanoma (UM), the most common intraocular tumor in adults. Mechanisms driving metabolic reprogramming in UM are poorly understood. Elucidation of these mechanisms could inform development of new therapeutic strategies for metastatic UM, which has poor prognosis because existing therapies are ineffective.

Characterization of Mycolic Acids by Multiple-Stage Linear Ion-Trap Mass Spectrometry.

(Mtb) cells are known to synthesize very long chain (C60-90) structurally complex mycolic acids with various functional groups. In this study, we applied linear ion-trap (LIT) multiple-stage mass spectrometry (MS), combined with high-resolution mass spectrometry to study the mechanisms underlying the fragmentation processes of mycolic acid standards desorbed as lithiated adduct ions by ESI. This is followed by structural characterization of a Mtb mycolic acid family (Bovine strain).

Mass Spectrometry-Based Shotgun Lipidomics Using Charge-Switch Derivatization for Analysis of Complex Long-Chain Fatty Acids.

Charge-switch derivatization to convert long-chain fatty acids (LCFAs) to their N-(4-aminomethylphenyl) pyridinium (AMPP) derivatives (FA-AMPP derivative) drastically increases their sensitivity (>10) detected by electrospray ionization (ESI) or matrix assisted laser desorption ionization (MALDI). Lipidomic analyses of the FA-AMPP derivatives by ESI combined with CID tandem mass spectrometry (MS), or by MALDI-TOF/TOF affords unambiguous structural characterization of LCFAs, including many unusual microbial LCFAs that contain various functional groups such as methyl, hydroxyl, cyclopropyl, and double bond(s). The ease of preparation of the FA-AMPP derivatives, the tremendous gain in sensitivity after derivatization, and more importantly, the readily recognizable product ion spectra that contain rich structurally informative fragment ions for locating functional groups make this method one of the most powerful techniques for LCFA identification and quantification.

Metabolic Effects of Selective Deletion of Group VIA Phospholipase A from Macrophages or Pancreatic Islet Beta-Cells.

To examine the role of group VIA phospholipase A (iPLAβ) in specific cell lineages in insulin secretion and insulin action, we prepared mice with a selective iPLAβ deficiency in cells of myelomonocytic lineage, including macrophages (MØ-iPLAβ-KO), or in insulin-secreting β-cells (β-Cell-iPLAβ-KO), respectively. MØ-iPLAβ-KO mice exhibited normal glucose tolerance when fed standard chow and better glucose tolerance than floxed-iPLAβ control mice after consuming a high-fat diet (HFD). MØ-iPLAβ-KO mice exhibited normal glucose-stimulated insulin secretion (GSIS) in vivo and from isolated islets ex vivo compared to controls.

Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts.

Cataracts are a major cause of blindness worldwide and commonly occur in individuals over 70 years old. Cataracts can also appear earlier in life due to genetic mutations. The lens proteins, αA- and αB-crystallins, are chaperone proteins that have important roles maintaining protein solubility to prevent cataract formation.

Lathosterol Oxidase (Sterol C-5 Desaturase) Deletion Confers Resistance to Amphotericin B and Sensitivity to Acidic Stress in Leishmania major.

Lathosterol oxidase (LSO) catalyzes the formation of the C-5-C-6 double bond in the synthesis of various types of sterols in mammals, fungi, plants, and protozoa. In parasites, mutations in or other sterol biosynthetic genes are associated with amphotericin B resistance. To investigate the biological roles of sterol C-5-C-6 desaturation, we generated an -null mutant line ( ) in , the causative agent for cutaneous leishmaniasis.

Correction to: Characterization of Long-Chain Fatty Acid as N-(4-Aminomethylphenyl) Pyridinium Derivative by MALDI LIFT-TOF/TOF Mass Spectrometry.

In the preceding article "Characterization of Long-Chain Fatty Acid as N-(4-Aminomethylphenyl) Pyridinium Derivative by MALDI LIFT-TOF/TOF Mass Spectrometry" by Frankfater et al., errors in Figs. 2 and 3 have occurred.

Characterization of Long-Chain Fatty Acid as N-(4-Aminomethylphenyl) Pyridinium Derivative by MALDI LIFT-TOF/TOF Mass Spectrometry.

Charge remote fragmentation (CRF) elimination of CH residues along the aliphatic tail of long chain fatty acid is hall mark of keV high-energy CID fragmentation process. It is an important fragmentation pathway leading to structural characterization of biomolecules by CID tandem mass spectrometry. In this report, we describe MALDI LIFT TOF-TOF mass spectrometric approach to study a wide variety of fatty acids (FAs), which were derivatized to N-(4-aminomethylphenyl) pyridinium (AMPP) derivative, and desorbed as M ions by laser with or without matrix.

Processing of a sesquiterpene lactone by Papilio glaucus caterpillars.

Papilio glaucus caterpillars encounter a diverse array of sesquiterpene lactones, including parthenolide, in the leaves of host plants Liriodendron tulipifera and Magnolia virginiana. These compounds are toxic to unadapted herbivores, and the development of P. glaucus caterpillars likely depends on their ability to excrete or detoxify them efficiently.