N. V. Krylov
St. Petersburg Math. J. 31 (2020), 509-520.
Abstract, references and article information

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.

Members Event

Event participants

Professor Sarah Cleveland, Louis Henkin Professor of Human and Constitutional Rights; Faculty Co-Director, Human Rights Institute, Columbia Law School

Amal Clooney, Barrister, Doughty Street Chambers

The Honourable Irwin Cotler, Chair, Raoul Wallenberg Centre for Human Rights; Minister of Justice and Attorney-General of Canada (2003-06)

Baroness Helena Kennedy QC, Director, International Bar Association’s Human Rights Institute

Lord Neuberger, President, Supreme Court of the United Kingdom (2012-17)

Maria Ressa, CEO, Rappler Online News Network

Chair: Elizabeth Wilmshurst CMG, Distinguished Fellow, International Law Programme, Chatham House

The canonical pathway of eicosanoid production in most mammalian cells is initiated by phospholipase A2-mediated release of arachidonic acid, followed by its enzymatic oxidation resulting in a vast array of eicosanoid products. However, recent work has demonstrated that the major phospholipase in mitochondria, iPLA2γ (patatin-like phospholipase domain containing 8 (PNPLA8)), possesses sn-1 specificity, with polyunsaturated fatty acids at the sn-2 position generating polyunsaturated sn-2-acyl lysophospholipids. Through strategic chemical derivatization, chiral chromatographic separation, and multistage tandem MS, here we first demonstrate that human platelet-type 12-lipoxygenase (12-LOX) can directly catalyze the regioselective and stereospecific oxidation of 2-arachidonoyl-lysophosphatidylcholine (2-AA-LPC) and 2-arachidonoyl-lysophosphatidylethanolamine (2-AA-LPE). Next, we identified these two eicosanoid-lysophospholipids in murine myocardium and in isolated platelets. Moreover, we observed robust increases in 2-AA-LPC, 2-AA-LPE, and their downstream 12-LOX oxidation products, 12(S)-HETE-LPC and 12(S)-HETE-LPE, in calcium ionophore (A23187)-stimulated murine platelets. Mechanistically, genetic ablation of iPLA2γ markedly decreased the calcium-stimulated production of 2-AA-LPC, 2-AA-LPE, and 12-HETE-lysophospholipids in mouse platelets. Importantly, a potent and selective 12-LOX inhibitor, ML355, significantly inhibited the production of 12-HETE-LPC and 12-HETE-LPE in activated platelets. Furthermore, we found that aging is accompanied by significant changes in 12-HETE-LPC in murine serum that were also markedly attenuated by iPLA2γ genetic ablation. Collectively, these results identify previously unknown iPLA2γ-initiated signaling pathways mediated by direct 12-LOX oxidation of 2-AA-LPC and 2-AA-LPE. This oxidation generates previously unrecognized eicosanoid-lysophospholipids that may serve as biomarkers for age-related diseases and could potentially be used as targets in therapeutic interventions.

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Invitation Only Research Event

Event participants

Maria Shagina, CEES Postdoctoral Fellow, Center for Eastern European Studies, University of Zurich
Chair: Richard Connolly, Associate Fellow, Russia and Eurasia Programme, Chatham House

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Shortly after reporting to Giants camp this week, Pablo Sandoval met with manager Bruce Bochy and reiterated his desire to help the club in whatever way he can.

Pablo Sandoval said he recruited his friends Gerardo Parra and Yangervis Solarte to the Giants in the offseason.

Members Event

Event participants

Professor Sarah Cleveland, Louis Henkin Professor of Human and Constitutional Rights; Faculty Co-Director, Human Rights Institute, Columbia Law School

Amal Clooney, Barrister, Doughty Street Chambers

The Honourable Irwin Cotler, Chair, Raoul Wallenberg Centre for Human Rights; Minister of Justice and Attorney-General of Canada (2003-06)

Baroness Helena Kennedy QC, Director, International Bar Association’s Human Rights Institute

Lord Neuberger, President, Supreme Court of the United Kingdom (2012-17)

Maria Ressa, CEO, Rappler Online News Network

Chair: Elizabeth Wilmshurst CMG, Distinguished Fellow, International Law Programme, Chatham House

19 December 2019

Permen Ailida Candy Obat Perangsang merupakan perangsang wanita herbal yang berbentu permen candy denga rasa manis seperti buah untuk meningkatkan gairah

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Obat Perangsang Libido Wanita Blue Wizard Adalah Obat Perangsang Wanita Alami Yang Berasal Dari Jerman, Sangat Manjur Untuk Wanita Kurang Bergairah (Firgid)

Invitation Only Research Event

Event participants

Maria Shagina, CEES Postdoctoral Fellow, Center for Eastern European Studies, University of Zurich
Chair: Richard Connolly, Associate Fellow, Russia and Eurasia Programme, Chatham House

Here are the top players in each league who could get the opportunity to show what they can do at the highest level this year, perhaps even contending for Rookie of the Year honors

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A vegetarian dish with a tasty side salad

Cold damp weather prompts all manner of mushrooms and fungi to emerge from the forest floor. Having neighbours willing to share their regular harvest of field mushrooms is one of the many great privileges of living in the Southern Forests. However, this hearty winter soup can be equally delicious when made with cultivated mushrooms easily purchased from supermarkets and independent grocers.

Delicious gourmet steak, onion and cheese sandwich

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400g ripe roma (plum) or pomodorino (baby plum) tomatoes 1 1/2 tablespoons chopped mint 1 teaspoon dried oregano 90g plain flour 1 teaspoon baking powder 1 teaspoon salt Light olive oil, or sunflower oil for pan-frying 250g Greek-style yogurt 1 tablespoon finely chopped dill Lemon wedges, to serve

4 x 150 x g of pork loin steaks as your butcher to cut 3 x cup (210 g) Panko Breadcrumbs (Japanese bread crumb) 1/2 cup (80g) Plain flour Chopped flat leaf parsley, thyme, rosemary 2 Eggs, lightly beaten 1/2cup (80g) finely grated Parmesan CABBAGE SLAW 500 grams of Cabbage finely shredded Squeezed of Lemon juice 1/4 cup (60 ml) quality cider vinegar add to taste. May need less. 2 Tablespoon of Macadamia Oil 1 Tablespoon chop parsley Aioli just a little bit to bind Sea salt and cracked pepper 100 ml Macadamia oil for cooking 4 juicy lemon wedges to squeeze over Pork

OBJECTIVE

This study aimed to reveal the associations between the risk of new-onset type 2 diabetes and the duration of antidepressant use and the antidepressant dose, and between antidepressant use after diabetes onset and clinical outcomes.

Farmers keep us fed and our economies stable, but in the US they're retiring faster than they're being replaced. Take a crash course in agricultural policy with Eric Sannerud to see why this problem can't be solved by simply buying from your local farmer's market -- and learn how you can use your vote to create a better future for farmers.

"Life's beauty is inseparable from its fragility," says psychologist Susan David. In a special virtual conversation, she shares wisdom on how to build resilience, courage and joy in the midst of the coronavirus pandemic. Responding to listeners' questions from across the globe, she offers ways to talk to your children about their emotions, keep focus during the crisis and help those working on the front lines. (This virtual conversation is part of the TED Connects series, hosted by head of TED Chris Anderson and current affairs curator Whitney Pennington Rodgers. Recorded March 23, 2020)

In Florida, Indiana, Kansas, North Carolina, Tennessee and Utah, Republicans are arguing that candidates for local and state school boards should run on party tickets.

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This book is a biography of Sandy and her great grand fathers life journey, through an inspirational spiritual connection, involving cellular memory and genetic DNA. It entails a story of forced assimilation on a culture, still not identified in the countries constitution. Survival, deception, manipulation and confusion regarding Colonisation. This is on a scale of mass deception from a democracy that claims, equality and equity to all. The letter of Patent making South Australia a Province in 1836, shows that Consciousness Raising is evolving through the resilience and visualisation of the' Original peoples' of this ancient land, seen through the eyes of Sandy.