LysoPC acyltransferase/PC transacylase activities in plant plasma membrane and plasma membrane-associated endoplasmic reticulum

<p>Abstract</p> <p>Background</p> <p>The phospholipids of the plant plasma membrane are synthesized in the endoplasmic reticulum (ER). The majority of these lipids reach the plasma membrane independently of the secretory vesicular pathway. Phospholipid delivery to the mitochondria and chloroplasts of plant cells also bypasses the secretory pathway and here it has been proposed that lysophospholipids are transported at contact sites between specific regions of the ER and the respective organelle, followed by lysophospholipid acylation in the target organelle. To test the hypothesis that a corresponding mechanism operates to transport phospholipids to the plasma membrane outside the secretory pathway, we investigated whether lysolipid acylation occurs also in the plant plasma membrane and whether this membrane, like the chloroplasts and mitochondria, is in close contact with the ER.</p> <p>Results</p> <p>The plant plasma membrane readily incorporated the acyl chain of acyl-CoA into phospholipids. Oleic acid was preferred over palmitic acid as substrate and acyl incorporation occurred predominantly into phosphatidylcholine (PC). Phospholipase A₂stimulated the reaction, as did exogenous lysoPC when administered in above critical micellar concentrations. AgNO₃was inhibitory. The lysophospholipid acylation reaction was higher in a membrane fraction that could be washed off the isolated plasma membranes after repeated freezing and thawing cycles in a medium with lowered pH. This fraction exhibited several ER-like characteristics. When plasma membranes isolated from transgenic <it>Arabidopsis </it>expressing green fluorescent protein in the ER lumen were observed by confocal microscopy, membranes of ER origin were associated with the isolated plasma membranes.</p> <p>Conclusion</p> <p>We conclude that a lysoPC acylation activity is associated with plant plasma membranes and cannot exclude a PC transacylase activity. It is highly plausible that the enzyme(s) resides in a fraction of the ER, closely associated with the plasma membrane, or in both. We suggest that this fraction might be the equivalent of the mitochondria associated membrane of ER origin that delivers phospholipids to the mitochondria, and to the recently isolated ER-derived membrane fraction that is in close contact with chloroplasts. The <it>in situ </it>function of the lysoPC acylation/PC transacylase activity is unknown, but involvement in lipid delivery from the ER to the plasma membrane is suggested.</p

Investigating commercially relevant packaging solutions to improve storage stability of mechanically filleted Atlantic mackerel (Scomber scombrus) produced under industrial conditions

This study investigated the efficacy of three commercially relevant packaging methods (vacuum with water glazing VAC-G; vacuum with seawater VAC-S; shatter-layer packaging SL) to improve frozen storage stability of mechanically filleted Atlantic mackerel at −\ua025\ua0\ub0C, in comparison to water glazing alone (GL) and storage as whole unglazed, block frozen fish. Besides proximate composition and pH of raw material, quality changes were analysed by free fatty acid content (FFA), water holding capacity (WHC), cooking yield, lipid oxidation (lipid hydroperoxides, PV; non-protein bound thiobarbituric acid reactive substances, TBARS) and sensory profiles of cooked samples after 3.5, 8, 10 and 12\ua0months of frozen storage. Vacuum-packaging was effective in mitigating the PV and TBARS as well as rancid odour and flavour. The inclusion of seawater in VAC-S altered the sensory textural attributes of the mackerel fillet to be more juicy, tender and soft and increased the attribute of salty flavour in the sample. SL delayed rancid odour and flavour by 2\ua0months compared to GL. Processing of mackerel under industrial conditions, including filleting, handling, double-freezing and glazing accelerated the formation of FFA as well as losses of WHC and cooking yield in the fillet regardless the packaging methods

Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising treatment strategy. However, several high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance. Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which promotes inhibition of both p53/MDM2 (murine double minute 2) and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA (reactivation of p53 and induction of tumor cell apoptosis) and protoporphyrin IX (PpIX). Ion mobility-mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions

Deliberation, Representation, Equity

"What can we learn about the development of public interaction in e-democracy from a drama delivered by mobile headphones to an audience standing around a shopping center in a Stockholm suburb? In democratic societies there is widespread acknowledgment of the need to incorporate citizens’ input in decision-making processes in more or less structured ways. But participatory decision making is balancing on the borders of inclusion, structure, precision and accuracy. To simply enable more participation will not yield enhanced democracy, and there is a clear need for more elaborated elicitation and decision analytical tools. This rigorous and thought-provoking volume draws on a stimulating variety of international case studies, from flood risk management in the Red River Delta of Vietnam, to the consideration of alternatives to gold mining in Roșia Montană in Transylvania, to the application of multi-criteria decision analysis in evaluating the impact of e-learning opportunities at Uganda's Makerere University. Editors Love Ekenberg (senior research scholar, International Institute for Applied Systems Analysis [IIASA], Laxenburg, professor of Computer and Systems Sciences, Stockholm University), Karin Hansson (artist and research fellow, Department of Computer and Systems Sciences, Stockholm University), Mats Danielson (vice president and professor of Computer and Systems Sciences, Stockholm University, affiliate researcher, IIASA) and Göran Cars (professor of Societal Planning and Environment, Royal Institute of Technology, Stockholm) draw innovative collaborations between mathematics, social science, and the arts. They develop new problem formulations and solutions, with the aim of carrying decisions from agenda setting and problem awareness through to feasible courses of action by setting objectives, alternative generation, consequence assessments, and trade-off clarifications. As a result, this book is important new reading for decision makers in government, public administration and urban planning, as well as students and researchers in the fields of participatory democracy, urban planning, social policy, communication design, participatory art, decision theory, risk analysis and computer and systems sciences.

Deliberation, Representation, Equity

"What can we learn about the development of public interaction in e-democracy from a drama delivered by mobile headphones to an audience standing around a shopping center in a Stockholm suburb? In democratic societies there is widespread acknowledgment of the need to incorporate citizens’ input in decision-making processes in more or less structured ways. But participatory decision making is balancing on the borders of inclusion, structure, precision and accuracy. To simply enable more participation will not yield enhanced democracy, and there is a clear need for more elaborated elicitation and decision analytical tools. This rigorous and thought-provoking volume draws on a stimulating variety of international case studies, from flood risk management in the Red River Delta of Vietnam, to the consideration of alternatives to gold mining in Roșia Montană in Transylvania, to the application of multi-criteria decision analysis in evaluating the impact of e-learning opportunities at Uganda's Makerere University. Editors Love Ekenberg (senior research scholar, International Institute for Applied Systems Analysis [IIASA], Laxenburg, professor of Computer and Systems Sciences, Stockholm University), Karin Hansson (artist and research fellow, Department of Computer and Systems Sciences, Stockholm University), Mats Danielson (vice president and professor of Computer and Systems Sciences, Stockholm University, affiliate researcher, IIASA) and Göran Cars (professor of Societal Planning and Environment, Royal Institute of Technology, Stockholm) draw innovative collaborations between mathematics, social science, and the arts. They develop new problem formulations and solutions, with the aim of carrying decisions from agenda setting and problem awareness through to feasible courses of action by setting objectives, alternative generation, consequence assessments, and trade-off clarifications. As a result, this book is important new reading for decision makers in government, public administration and urban planning, as well as students and researchers in the fields of participatory democracy, urban planning, social policy, communication design, participatory art, decision theory, risk analysis and computer and systems sciences.

BETWEEN BROADCASTING POLITICAL MESSAGES AND INTERACTING WITH VOTERS

Politicians across Western democracies are increasingly adopting and experimenting with Twitter, particularly during election time. The purpose of this article is to investigate how candidates are using it during an election campaign. The aim is to create a typology of the various ways in which candidates behaved on Twitter. Our research, which included a content analysis of tweets (n = 26,282) from all twittering Conservative, Labour and Liberal Democrat candidates (n = 416) during the 2010 UK General Election campaign, focused on four aspects of tweets: type, interaction, function and topic. By examining candidates' twittering behaviour, the authors show that British politicians mainly used Twitter as a unidirectional form of communication. However, there were a group of candidates who used it to interact with voters by, for example, mobilizing, helping and consulting them, thus tapping into the potential Twitter offers for facilitating a closer relationship with citizens

Goettingen Minipigs (GMP): Comparison of Two Different Models for Inducing Diabetes

Purpose: Preclinical experiments on large animals are indispensable for evaluating the effectiveness of diabetes therapies. Miniature swine are well suited for such studies due to their physiological and pathophysiological responses. Methods: We compare two methods for inducing diabetes in Goettingen minipigs (GMP), in five with the beta cell toxin streptozotocin (STZ) and in five other GMP by total pancreatectomy (PE). Glucose homeostasis was assessed with the intravenous glucose-tolerance test (IVGTT) and continual monitoring of interstitial glucose levels. At conclusion of the observation period, the pancreata were examined histologically. Three non-diabetic GMP served as control group. Results: The IVGTT revealed markedly diabetic profiles in both GMP groups. STZ-GMP were found to harbor residual C-peptides and scattered insulin-positive cells in the pancreas. PE-GMP survived the total pancreatectomy only with intensive postoperative care. Conclusions: Although both methods reliably induced diabetes in GMP, the PE-GMP clearly had more health problems and required a greater expenditure of time and resources. The PE-GMP model, however, was better at eliminating endogenous insulin and C-peptide than the STZ-GMP model