ATP release via anion channels

ATP serves not only as an energy source for all cell types but as an ‘extracellular messenger-for autocrine and paracrine signalling. It is released from the cell via several different purinergic signal efflux pathways. ATP and its Mg2+ and/or H+ salts exist in anionic forms at physiological pH and may exit cells via some anion channel if the pore physically permits this. In this review we survey experimental data providing evidence for and against the release of ATP through anion channels. CFTR has long been considered a probable pathway for ATP release in airway epithelium and other types of cells expressing this protein, although non-CFTR ATP currents have also been observed. Volume-sensitive outwardly rectifying (VSOR) chloride channels are found in virtually all cell types and can physically accommodate or even permeate ATP4- in certain experimental conditions. However, pharmacological studies are controversial and argue against the actual involvement of the VSOR channel in significant release of ATP. A large-conductance anion channel whose open probability exhibits a bell-shaped voltage dependence is also ubiquitously expressed and represents a putative pathway for ATP release. This channel, called a maxi-anion channel, has a wide nanoscopic pore suitable for nucleotide transport and possesses an ATP-binding site in the middle of the pore lumen to facilitate the passage of the nucleotide. The maxi-anion channel conducts ATP and displays a pharmacological profile similar to that of ATP release in response to osmotic, ischemic, hypoxic and salt stresses. The relation of some other channels and transporters to the regulated release of ATP is also discussed

Enantioselective Arbuzov Reaction Enabled by Catalytic Ion-Pair Reorganization

The stereocontrolled synthesis of stereogenic-at-phosphorus compounds is a long-standing challenge in organic chemistry that has received heightened research attention in recent years. None of the catalytic approaches taken to date have leveraged the rich manifold of transformations proceeding through nucleophilic dealkylation of phosphonium ion intermediates (e.g. Michaelis–Arbuzov, Pudovik, and Appel reactions). Here, we report enantioselective hydrogen-bond-donor-catalyzed Michaelis–Arbuzov reactions of dialkylphosphonites with hydrogen chloride to afford H-phosphinates, which are versatile P-chiral building blocks. Mechanistic and computational investigations reveal that the catalyst diminishes the reactivity of the chloride nucleophile, yet accelerates the rate-determining dealkylation step by preorganizing the phosphonium chloride resting state into a geometry that is primed to enter the SN2 transition state

Efficient data retrieval for large-scale smart city applications through applied bayesian interference

Abstract—Recent years have witnessed the proliferation of worldwide efforts towards developing technologies for enabling smart cities, to improve the quality of life for citizens. These smart city solutions are typically deployed across large spatial regions over long time scales, generating massive volumes of data. An efficient way of data retrieval is thus required, for post-processing of the data- such as for analytical and visualization purposes. In this paper, we propose a data prefetching and caching algorithm based on Bayesian inference, for the retrieval of data in large-scale smart city applications. A brute-force approach is used to determine the optimal weight correction factor in the proposed prefetching algorithm. We evaluate the optimized Bayesian prefetching algorithm against the Naı̈ve and Random prefetch baselines, using both simulated and actual data usage patterns. Results show that the Bayesian approach can achieve up to 48.4 % reductions in actual user-perceived application delays during data retrieval. I

Morphological Annotation of a Corpus with a Collaborative Multiplayer Game

In most of the natural language processing tasks, state-ofthe-art systems usually rely on machine learning methods for building their mathematical models. Given that the majority of these systems employ supervised learning strategies, a corpus that is annotated for the problem area is essential. The current method for annotating a corpus is to hire several experts and make them annotate the corpus manually or by using a helper software. However, this method is costly and timeconsuming. In this paper, we propose a novel method that aims to solve these problems. By employing a multiplayer collaborative game that is playable by ordinary people on the Internet, it seems possible to direct the covert labour force so that people can contribute by just playing a fun game. Through a game site which incorporates some functionality inherited from social networking sites, people are motivated to contribute to the annotation process by answering questions about the underlying morphological features of a target word. The experiments show that the 63.5 % of the actual question types are successful based on a two-phase evaluation

Flavonoids as detoxifying and pro-survival agents: What's new?

The role of flavonoids in the survival machinery of cells has come in the spotlight due to the recent evidence of their effect on the relationship mitochondria-ER stress-proteasome, including the intracellular mechanisms of autophagy and apoptosis. Numerous experimental animal investigations and even human clinical studies have highlighted the major role of these natural compounds in the economy of life and their deep relationship with autotrophic organisms in the evolutionary space. Their role as anti-oxidant and oxidative stress preventive molecules has to date been investigated extensively in the literature. Despite this great amount of promising evidence, many concerns, however, remain, most of which dealing with biochemistry, bioavailability, pharmacokinetics, and interaction of flavonoids with gut microbiome, issues that make difficult any good attempt to introduce these molecules in the human healthcare systems as possible, encouraging therapeutic substances. This review tries to address and elucidate these items