Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Prehibernation diet and reproductive condition of female Anopheles messeae in Sweden

1. Blood and sugar feeding in the mosquito Anopheles messeae Falleroni were investigated near Uppsala, Sweden, from 1981 to 1985, with emphasis on prehibernation diet. 2. Fructose, indicating plant feeding, was present in females of all ovarian stages, from April to October, and contributed to fat body development in non-gonoactive females before hibernation. 3. An.messeae males and females (inseminated and uninseminated) were observed feeding on floral nectaries of the plants Achillea millefolium L. and Tanacetum vulgare L. at night during August. 4. Gonotrophic dissociation started in some females in July, and by the end of September all females were inseminated and nulliparous but non-gonoactive. 5. Animal sheds were used as diurnal resting sites of non-gonoactive, prehibernating female An.messeae. Among recently fed mosquitoes in that group, 85% were gut positive for fructose and 15% for blood. Most of them showed negative host tropism, indicating that bloodfeeding is not a prerequisite for hibernation. 6. Survival rates of bloodfed (48 +/- 31 days) and non-bloodfed (42 +/- 21 days) females, collected from a cattle shed in September and kept caged without food or water in a store house, were not significantly different. This indicates that bloodfeeding may occur facultatively before hibernation but does not affect longevity and survival. 7. If overwintering is possible for bloodfed An.messeae females, they would be more likely vectors of pathogens such as Batai virus.     

Deep-lipidotyping by mass spectrometry: recent technical advances and applications

In-depth structural characterization of lipids is an essential component of lipidomics. There has been a rapid expansion of mass spectrometry methods that are capable of resolving lipid isomers at various structural levels over the past decade. These developments finally make deep-lipidotyping possible, which provides new means to study lipid metabolism and discover new lipid biomarkers. In this review, we discuss recent advancements in tandem mass spectrometry (MS/MS) methods for identification of complex lipids beyond the species (known headgroup information) and molecular species (known chain composition) levels. These include identification at the levels of carbon-carbon double bond (C=C) location and sn-position, as well as characterization of acyl chain modifications. We also discuss the integration of isomer-resolving MS/MS methods with different lipid analysis workflows and their applications in lipidomics. The results showcase the distinct capabilities of deep-lipidotyping in untangling the metabolism of individual isomers and sensitive phenotyping by using relative fractional quantitation of the isomers.     

Structural determinants of multimerization and dissociation in 2-Cys peroxiredoxin chaperone function

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Sequentially Deposited versus Conventional Nonfullerene Organic Solar Cells: Interfacial Trap States,Vertical Stratification,and Exciton Dissociation

Bulk heterojunction (BHJ) nonfullerene organic solar cells prepared from sequentially deposited donor and acceptor layers (sq‐BHJ) have recently been shown to be highly efficient, environmentally friendly, and compatible with large area and roll‐to‐roll fabrication. However, the related photophysics at donor‐acceptor interface and the vertical heterogeneity of donor‐acceptor distribution, critical for exciton dissociation and device performance, have been largely unexplored. Herein, steady‐state and time‐resolved optical and electrical techniques are employed to characterize the interfacial trap states. Correlating with the luminescent efficiency of interfacial states and its nonradiative recombination, interfacial trap states are characterized to be about 40% more populated in the sq‐BHJ devices than the as‐cast BHJ (c‐BHJ), which probably limits the device voltage output. Cross‐sectional energy‐dispersive X‐ray spectroscopy and ultraviolet photoemission spectroscopy depth profiling directly visualize the donor–acceptor vertical stratification with a precision of 1–2 nm. From the proposed “needle” model, the high exciton dissociation efficiency is rationalized. This study highlights the promise of sequential deposition to fabricate efficient solar cells, and points toward improving the voltage output and overall device performance via eliminating interfacial trap states.     

Sequential Ubiquitination of Ribosomal Protein uS3 Triggers the Degradation of Non-functional 18S rRNA

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Allostery mediates ligand binding to WWOX tumor suppressor via a conformational switch

While being devoid of the ability to recognize ligands itself, the WW2 domain is believed to aid ligand binding to the WW1 domain in the context of a WW1–WW2 tandem module of WW domain‐containing oxidoreductase (WWOX) tumor suppressor. In an effort to test the generality of this hypothesis, we have undertaken here a detailed biophysical analysis of the binding of WW domains of WWOX alone and in the context of the WW1–WW2 tandem module to an array of putative proline‐proline‐x–tyrosine (PPXY) ligands. Our data show that while the WW1 domain of WWOX binds to all ligands in a physiologically relevant manner, the WW2 domain does not. Moreover, ligand binding to the WW1 domain in the context of the WW1–WW2 tandem module is two‐to‐three‐fold stronger than when treated alone. We also provide evidence that the WW domains within the WW1–WW2 tandem module physically associate so as to adopt a fixed spatial orientation relative to each other. Of particular note is the observation that the physical association of the WW2 domain with WW1 blocks access to ligands. Consequently, ligand binding to the WW1 domain not only results in the displacement of the WW2 lid but also disrupts the physical association of WW domains in the liganded conformation. Taken together, our study underscores a key role of allosteric communication in the ability of the WW2 orphan domain to chaperone physiological action of the WW1 domain within the context of the WW1–WW2 tandem module of WWOX. Copyright © 2015 John Wiley & Sons, Ltd.     

Top-down mass spectrometry of intact membrane protein complexes reveals oligomeric state and sequence information in a single experiment

Here we study the intact stoichiometry and top-down fragmentation behavior of three integral membrane proteins which were natively reconstituted into detergent micelles: the mechano-sensitive ion channel of large conductance (MscL), the Kirbac potassium channel and the p7 viroporin from the hepatitis C virus. By releasing the proteins under nondenaturing conditions inside the mass spectrometer, we obtained their oligomeric sizes. Increasing the ion activation (collision energy) causes unfolding and subsequent ejection of a highly charged monomer from the membrane protein complexes. Further increase of the ion activation then causes collision-induced dissociation (CID) of the ejected monomers, with fragments observed which were predominantly found to stem from membrane-embedded regions. These experiments show how in a single experiment, we can probe the relation between higher-order structure and protein sequence, by combining the native MS data with fragmentation obtained from top-down MS.     

The mechanisms of defense and dreaming.

This study examined the degree to which the phenomenological experience of dream intensity and its components are correlated with repression, splitting, and other defense mechanisms. The Dream Intensity Scale, Marlowe-Crowne Social Desirability Scale, Splitting Scale, Defense Style Questionnaire-40, and other related measures were administered to 583 subjects. It is demonstrated that repression as a personality trait is inversely and moderately related to the quantitative aspect of dream intensity (i.e., frequencies of dream awareness, nightmares, and multiple dreams in a single night) but does not influence qualitative sensory experiences in dreams (e.g., hearing sounds in dreams). Moreover, the present findings indicate that the more repressed people are, the less likely they are to report splitting and immature defenses, and the less frequently they experience dreams, with the effect of repression on defenses being greater than that on dream intensity. Accordingly, if both dreams and defense mechanisms are the critical materials to work through in a treatment, then starting with the former may be conducive to the therapeutic progress by provoking less resistance from the client. (PsycINFO Database Record (c) 2011 APA, all rights reserved)