Physiological Fatty Acid-Stimulated Insulin Secretion and Redox Signaling Lipotoxicity.

Type 2 diabetes as a world-wide epidemic is characterized by the insulin resistance concomitant to a gradual impairment of β-cell mass and function (prominently declining insulin secretion) with dysregulated fatty acids (FAs) and lipids, all involved in multiple pathological development. Recently, redox signaling was recognized to be essential for insulin secretion stimulated with glucose (GSIS), branched-chain keto-acids, and FAs. FA-stimulated insulin secretion (FASIS) is a normal physiological event upon postprandial incoming chylomicrons.

Mitochondria to plasma membrane redox signaling is essential for fatty acid β-oxidation-driven insulin secretion.

We asked whether acute redox signaling from mitochondria exists concomitantly to fatty acid- (FA-) stimulated insulin secretion (FASIS) at low glucose by pancreatic β-cells. We show that FA β-oxidation produces superoxide/HO, providing: i) mitochondria-to-plasma-membrane redox signaling, closing K-channels synergically with elevated ATP (substituting NADPH-oxidase-4-mediated HO-signaling upon glucose-stimulated insulin secretion); ii) activation of redox-sensitive phospholipase iPLAγ/PNPLA8, cleaving mitochondrial FAs, enabling metabotropic GPR40 receptors to amplify insulin secretion (IS). At fasting glucose, palmitic acid stimulated IS in wt mice; palmitic, stearic, lauric, oleic, linoleic, and hexanoic acids also in perifused pancreatic islets (PIs), with suppressed 1st phases in iPLAγ/PNPLA8-knockout mice/PIs.

Mitochondrial dynamics: updates and perspectives.

Mitochondria, the powerhouse and the vital signaling hub of the cell, participate in a variety of biological processes, such as apoptosis, redox responses, cell senescence, autophagy, and iron homeostasis. Mitochondria form a mostly tubular network, made up of an outer and a cristeae-forming inner membrane. The network undergoes dynamic fusion and fission that change its morphological structure according to the functional needs.

BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria.

Background: Pancreatic ductal adenocarcinoma (PDAC) has been associated with the host dysmetabolism of branched-chain amino acids (BCAAs), however, the implications for the role of BCAA metabolism in PDAC development or progression are not clear. The mitochondrial catabolism of valine, leucine, and isoleucine is a multistep process leading to the production of short-chain R-CoA species. They can be subsequently exported from mitochondria as short-chain carnitines (SC-CARs), utilized in anabolic pathways, or released from the cells.

Two mitochondrial DNA polymorphisms modulate cardiolipin binding and lead to synthetic lethality.

Genetic screens have been used extensively to probe interactions between nuclear genes and their impact on phenotypes. Probing interactions between mitochondrial genes and their phenotypic outcome, however, has not been possible due to a lack of tools to map the responsible polymorphisms. Here, using a toolkit we previously established in Drosophila, we isolate over 300 recombinant mitochondrial genomes and map a naturally occurring polymorphism at the cytochrome c oxidase III residue 109 (CoIII) that fully rescues the lethality and other defects associated with a point mutation in cytochrome c oxidase I (CoI).

NADPH oxidase 4 in mouse β cells participates in inflammation on chronic nutrient overload.

Objective: By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4-/-) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype.

Methods: The authors performed basic phenotyping of βNOX4-/- mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages.

Pitfalls of Mitochondrial Redox Signaling Research.

Redox signaling from mitochondria (mt) to the cytosol and plasma membrane (PM) has been scarcely reported, such as in the case of hypoxic cell adaptation or (2-oxo-) 2-keto-isocaproate (KIC) β-like-oxidation stimulating insulin secretion in pancreatic β-cells. Mutual redox state influence between mitochondrial major compartments, the matrix and the intracristal space, and the cytosol is therefore derived theoretically in this article to predict possible conditions, when mt-to-cytosol and mt-to-PM signals may occur, as well as conditions in which the cytosolic redox signaling is not overwhelmed by the mitochondrial antioxidant capacity. Possible peroxiredoxin 3 participation in mt-to-cytosol redox signaling is discussed, as well as another specific case, whereby mitochondrial superoxide release is diminished, whereas the matrix MnSOD is activated.

Mitochondrial Dynamics and Cristae Shape Changes During Metabolic Reprogramming.

The architecture of the mitochondrial network and cristae critically impact cell differentiation and identity. Cells undergoing metabolic reprogramming to aerobic glycolysis (Warburg effect), such as immune cells, stem cells, and cancer cells, go through controlled modifications in mitochondrial architecture, which is critical for achieving the resulting cellular phenotype. Recent studies in immunometabolism have shown that the manipulation of mitochondrial network dynamics and cristae shape directly affects T cell phenotype and macrophage polarization through altering energy metabolism.

Possible frequent multiple mitochondrial DNA copies in a single nucleoid in HeLa cells.

Previously, a number of ~ 1.4 of mitochondrial DNA (mtDNA) molecules in a single nucleoid was reported, which would reflect a minimum nucleoid division. We applied 3D-double-color direct stochastic optical reconstruction microscopy (dSTORM), i.

Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology.

Mitochondrial (mt) reticulum network in the cell possesses amazing ultramorphology of parallel lamellar cristae, formed by the invaginated inner mitochondrial membrane. Its non-invaginated part, the inner boundary membrane (IBM) forms a cylindrical sandwich with the outer mitochondrial membrane (OMM). Crista membranes (CMs) meet IBM at crista junctions (CJs) of mt cristae organizing system (MICOS) complexes connected to OMM sorting and assembly machinery (SAM).

[Case report of fatal sepsis caused by Actinobacillus suis/equuli in an adult male].

This is a case report of sepsis caused by the species Actinobacillus suis/equuli in a male agriculture worker that ended fatally. The article also contains information on identification and results of antibiotic susceptibility testing. This is a rare case of human infection and probably the first case of a human being infected by this species in the Czech Republic.

Poly(4-Styrenesulfonic Acid--maleic Anhydride)-Coated NaGdF:Yb,Tb,Nd Nanoparticles with Luminescence and Magnetic Properties for Imaging of Pancreatic Islets and β-Cells.

Novel Yb,Tb,Nd-doped GdF and NaGdF nanoparticles were synthesized by a coprecipitation method in ethylene glycol (EG) in the presence of the poly(4-styrenesulfonic acid--maleic anhydride) stabilizer. The particle size and morphology, crystal structure, and phase change were controlled by adjusting the PSSMA concentration and source of fluoride anions in the reaction. Doping of Yb, Tb, and Nd ions in the NaGdF host nanoparticles induced luminescence under ultraviolet and near-infrared excitation and high relaxivity in magnetic resonance (MR) imaging (MRI).

[Pseudotuberculosis - a case report of gastroenteritis in a five-year-old boy].

The article describes a case of a rare infection caused by Yersinia pseudotuberculosis in a five-year-old boy admitted to the hospital. The infection was manifested by the so-called right lower quadrant syndrome, or terminal ileitis. The Y.

Antioxidant Role and Cardiolipin Remodeling by Redox-Activated Mitochondrial Ca-Independent Phospholipase Aγ in the Brain.

Mitochondrial Ca-independent phospholipase Aγ (iPLAγ/PNPLA8) was previously shown to be directly activated by HO and release free fatty acids (FAs) for FA-dependent H transport mediated by the adenine nucleotide translocase (ANT) or uncoupling protein 2 (UCP2). The resulting mild mitochondrial uncoupling and consequent partial attenuation of mitochondrial superoxide production lead to an antioxidant effect. However, the antioxidant role of iPLAγ in the brain is not completely understood.

Mitochondrial Redox Regulations and Redox Biology of Mitochondria.

Mitochondria undoubtedly represent a metabolic hub, but also act as a redox hub, controlling cell fate and emanating superoxide/HO, which in a regulated form and timing provide redox signaling [...

Poly(N,N-dimethylacrylamide)-coated upconverting NaYF:Yb,Er@NaYF:Nd core-shell nanoparticles for fluorescent labeling of carcinoma cells.

Upconverting luminescent lanthanide-doped nanoparticles (UCNP) belong to promising new materials that absorb infrared light able to penetrate in the deep tissue level, while emitting photons in the visible or ultraviolet region, which makes them favorable for bioimaging and cell labeling. Here, we have prepared upconverting NaYF:Yb,Er@NaYF:Nd core-shell nanoparticles, which were coated with copolymers of N,N-dimethylacrylamide (DMA) and 2-(acryloylamino)-2-methylpropane-1-sulfonic acid (AMPS) or tert-butyl [2-(acryloylamino)ethyl]carbamate (AEC-Boc) with negative or positive charges, respectively. The copolymers were synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization, reaching M ~ 11 kDa and containing ~ 5 mol% of reactive groups.

Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.

Mitochondria determine glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells by elevating ATP synthesis. As the metabolic and redox hub, mitochondria provide numerous links to the plasma membrane channels, insulin granule vesicles (IGVs), cell redox, NADH, NADPH, and Ca homeostasis, all affecting insulin secretion. Mitochondrial redox signaling was implicated in several modes of insulin secretion (branched-chain ketoacid [BCKA]-, fatty acid [FA]-stimulated).

Antioxidant Synergy of Mitochondrial Phospholipase PNPLA8/iPLA2γ with Fatty Acid-Conducting SLC25 Gene Family Transporters.

Patatin-like phospholipase domain-containing protein PNPLA8, also termed Ca-independent phospholipase A2γ (iPLA2γ), is addressed to the mitochondrial matrix (or peroxisomes), where it may manifest its unique activity to cleave phospholipid side-chains from both sn-1 and sn-2 positions, consequently releasing either saturated or unsaturated fatty acids (FAs), including oxidized FAs. Moreover, iPLA2γ is directly stimulated by HO and, hence, is activated by redox signaling or oxidative stress. This redox activation permits the antioxidant synergy with mitochondrial uncoupling proteins (UCPs) or other SLC25 mitochondrial carrier family members by FA-mediated protonophoretic activity, termed mild uncoupling, that leads to diminishing of mitochondrial superoxide formation.

Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma.

Mitochondrial production of 2-hydroxyglutarate (2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we quantified 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics.

The Pancreatic β-Cell: The Perfect Redox System.

Pancreatic β-cell insulin secretion, which responds to various secretagogues and hormonal regulations, is reviewed here, emphasizing the fundamental redox signaling by NADPH oxidase 4- (NOX4-) mediated HO production for glucose-stimulated insulin secretion (GSIS). There is a logical summation that integrates both metabolic plus redox homeostasis because the ATP-sensitive K channel (K) can only be closed when both ATP and HO are elevated. Otherwise ATP would block K, while HO would activate any of the redox-sensitive nonspecific calcium channels (NSCCs), such as TRPM2.

Colloidally Stable P(DMA-AGME)-Ale-Coated Gd(Tb)F:Tb(Gd),Yb,Nd Nanoparticles as a Multimodal Contrast Agent for Down- and Upconversion Luminescence, Magnetic Resonance Imaging, and Computed Tomography.

Multimodal imaging, integrating several modalities including down- and up-conversion luminescence, - and ( *)-weighted MRI, and CT contrasting in one system, is very promising for improved diagnosis of severe medical disorders. To reach the goal, it is necessary to develop suitable nanoparticles that are highly colloidally stable in biologically relevant media. Here, hydrophilic poly(,-dimethylacrylamide--acryloylglycine methyl ester)-alendronate-[P(DMA-AGME)-Ale]-coated Gd(Tb)F:Tb(Gd),Yb,Nd nanoparticles were synthesized by a coprecipitation method in ethylene glycol (EG) followed by coating with the polymer.

[Unusual microbiological findings in bacteremia cases - three case reports].

The authors present three case reports of bacteremia with very rare microorganisms being isolated in the patients. Each brief case report is accompanied by etiological considerations related to the diagnosis and clinical condition of the patient. Routine microbiology tests were performed by examining the biochemical properties using commercial kits.

[Our experiences with Actinomyces urogenitalis in human clinical samples].

Actinomyces urogenitalis is most commonly associated with the human genitourinary system, often only as the resident flora. Outside the genitourinary tract, A. urogenitalis is isolated rather sporadically.

NWB Query Engines: Tools to Search Data Stored in Neurodata Without Borders Format.

The Neurodata Without Borders (abbreviation NWB) format is a current technology for storing neurophysiology data along with the associated metadata. Data stored in the format is organized into separate HDF5 files, each file usually storing the data associated with a single recording session. While the NWB format provides a structured method for storing data, so far there have not been tools which enable searching a collection of NWB files in order to find data of interest for a particular purpose.