AdS weight shifting operators Costa, Miguel S.; Hansen, Tobias
The journal of high energy physics,
09/2018, Letnik:
2018, Številka:
9
Journal Article
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A
bstract
We construct a new class of differential operators that naturally act on AdS harmonic functions. These are weight shifting operators that change the spin and dimension of AdS ...representations. Together with CFT weight shifting operators, the new operators obey crossing equations that relate distinct representations of the conformal group. We apply our findings to the computation of Witten diagrams, focusing on the particular case of cubic interactions and on massive, symmetric and traceless fields. In particular we show that tree level 4-point Witten diagrams with arbitrary spins, both in the external fields and in the exchanged field, can be reduced to the action of weight shifting operators on similar 4-point Witten diagrams where all fields are scalars. We also show how to obtain the conformal partial wave expansion of these diagrams using the new set of operators. In the case of 1-loop diagrams with cubic couplings we show how to reduce them to similar 1-loop diagrams with scalar fields except for a single external spinning field (which must be a scalar in the case of a two-point diagram). As a bonus, we provide new CFT and AdS weight shifting operators for mixed-symmetry tensors.
•Coffee silverskin is very rich in insoluble fibre (49%).•Potassium, magnesium and calcium are major macrominerals of silverskin.•The vitamin E profile of silverskin comprises seven ...vitamers.•Silverskin extracts protected erythrocytes from oxidative induced hemolysis,•At higher extract concentrations a pro-oxidant effect was observed.
Coffee silverskin (a coffee roasting by-product) contains high amounts of dietary fibre (49% insoluble and 7% soluble) and protein (19%). Potassium (∼5g/100g), magnesium (2g/100g) and calcium (0.6g/100g) are the major macrominerals. The vitamin E profile of silverskin comprises α-tocopherol, β-tocopherol, ɣ-tocopherol, δ-tocopherol, β-tocotrienol, ɣ-tocotrienol, and δ-tocotrienol. The fatty acid profile is mainly saturated (C16:0 and C22:0), but the total amount of fat is low (2.4%). Caffeine (1.25g/100g), chlorogenic acid (246mg/100g), and 5-hydroxymethylfurfural (5.68mg/100g) are also present in silverskin. Total phenolics and flavonoids are partially responsible for the in vitro antioxidant activity. Silverskin extracts protected erythrocytes from oxidative AAPH- and H2O2-induced hemolysis, but at high concentrations a pro-oxidant effect on erythrocyte morphology was observed.
Abstract Sulfated polysaccharides from 11 species of tropical marine algae (one edible specie of Rhodophyta, six species of Phaeophyta and four species of Chlorophyta) collected from Natal city coast ...(Northeast of Brazil) were evaluated for their anticoagulant, antioxidant and antiproliverative in vitro activities. In the activated partial thromboplastin time (APTT) test, which evaluates the intrinsic coagulation pathway, seven seaweeds presented anticoagulant activity. Dictyota cervicornis showed the highest activity, prolonging the coagulation time to double the baseline value in the APTT with only 0.01 mg/100 μl of plasma, 1.4-fold lesser than Clexane® , a low molecular weight heparin. In the protrombin time (PT) test, which evaluates the extrinsic coagulation pathway, only Caulerpa cupresoides showed anticoagulant activity. All species collected showed antioxidant activities. This screening emphasized the great antioxidant potential (total capacity antioxidant, power reducing and ferrous chelating) of four species: C. sertularioide ; Dictyota cervicornis; Sargassum filipendula and Dictyopteris delicatula . After 72 h incubation, HeLa cell proliferation was inhibited ( p < 0.05) between 33.0 and 67.5% by S. filipendula ; 31.4 and 65.7% by D. delicatula ; 36.3 and 58.4% by Caulerpa prolifera and 40.2 and 61.0% by Dictyota menstrualis at 0.01–2 mg/mL algal polysaccharides. The antiproliferative efficacy of these algal polysaccharides were positively correlated with the sulfate content ( r = 0.934). Several polysaccharides demonstrated promising antioxidant, antiproliferative an/or anticoagulant potential and have been selected for further studies on bioguided fractionation, isolation and characterization of pure polysaccharides from these species as well as in vivo experiments are needed and are already in progress.
Exposure to stress during early life (infancy/childhood) has long-term effects on the structure and function of the prefrontal cortex (PFC), and increases the risk for adult depression and anxiety ...disorders. However, little is known about the molecular and cellular mechanisms of these effects. Here, we focused on changes induced by chronic maternal separation during the first 2 weeks of postnatal life. Unbiased mRNA expression profiling in the medial PFC (mPFC) of maternally separated (MS) pups identified an increased expression of myelin-related genes and a decreased expression of immediate early genes. Oligodendrocyte lineage markers and birthdating experiments indicated a precocious oligodendrocyte differentiation in the mPFC at P15, leading to a depletion of the oligodendrocyte progenitor pool in MS adults. We tested the role of neuronal activity in oligodendrogenesis, using designed receptors exclusively activated by designed drugs (DREADDs) techniques. hM4Di or hM3Dq constructs were transfected into mPFC neurons using fast-acting AAV8 viruses. Reduction of mPFC neuron excitability during the first 2 postnatal weeks caused a premature differentiation of oligodendrocytes similar to the MS pups, while chemogenetic activation normalised it in the MS animals. Bidirectional manipulation of neuron excitability in the mPFC during the P2-P14 period had long lasting effects on adult emotional behaviours and on temporal object recognition: hM4Di mimicked MS effects, while hM3Dq prevented the pro-depressive effects and short-term memory impairment of MS. Thus, our results identify neuronal activity as a critical target of early-life stress and demonstrate its function in controlling both postnatal oligodendrogenesis and adult mPFC-related behaviours.
The critical stem cell transcription factor FoxD3 is expressed by the premigratory and migrating neural crest, an embryonic stem cell population that forms diverse derivatives. Despite its important ...role in development and stem cell biology, little is known about what mediates FoxD3 activity in these cells. We have uncovered two FoxD3 enhancers, NC1 and NC2, that drive reporter expression in spatially and temporally distinct manners. Whereas NC1 activity recapitulates initial FoxD3 expression in the cranial neural crest, NC2 activity recapitulates initial FoxD3 expression at vagal/trunk levels while appearing only later in migrating cranial crest. Detailed mutational analysis, in vivo chromatin immunoprecipitation, and morpholino knock-downs reveal that transcription factors Pax7 and Msx1/2 cooperate with the neural crest specifier gene, Ets1, to bind to the cranial NC1 regulatory element. However, at vagal/trunk levels, they function together with the neural plate border gene, Zic1, which directly binds to the NC2 enhancer. These results reveal dynamic and differential regulation of FoxD3 in distinct neural crest subpopulations, suggesting that heterogeneity is encrypted at the regulatory level. Isolation of neural crest enhancers not only allows establishment of direct regulatory connections underlying neural crest formation, but also provides valuable tools for tissue specific manipulation and investigation of neural crest cell identity in amniotes.
Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic ...tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies.
Endothelial cells (ECs) adapt their metabolism to enable the growth of new blood vessels, but little is known how ECs regulate metabolism to adopt a quiescent state. Here, we show that the metabolite ...S-2-hydroxyglutarate (S-2HG) plays a crucial role in the regulation of endothelial quiescence. We find that S-2HG is produced in ECs after activation of the transcription factor forkhead box O1 (FOXO1), where it limits cell cycle progression, metabolic activity and vascular expansion. FOXO1 stimulates S-2HG production by inhibiting the mitochondrial enzyme 2-oxoglutarate dehydrogenase. This inhibition relies on branched-chain amino acid catabolites such as 3-methyl-2-oxovalerate, which increase in ECs with activated FOXO1. Treatment of ECs with 3-methyl-2-oxovalerate elicits S-2HG production and suppresses proliferation, causing vascular rarefaction in mice. Our findings identify a metabolic programme that promotes the acquisition of a quiescent endothelial state and highlight the role of metabolites as signalling molecules in the endothelium.
Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this ...pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents.
Advancement of DNA sequencing technology allows the routine use of genome sequences in the various fields of microbiology. The information held in genome sequences proved to provide objective and ...reliable means in the taxonomy of prokaryotes. Here, we describe the minimal standards for the quality of genome sequences and how they can be applied for taxonomic purposes.
Leakage of the blood–brain barrier (BBB) is associated with various neurological disorders, including temporal lobe epilepsy (TLE). However, it is not known whether alterations of the BBB occur ...during epileptogenesis and whether this can affect progression of epilepsy. We used both human and rat epileptic brain tissue and determined BBB permeability using various tracers and albumin immunocytochemistry. In addition, we studied the possible consequences of BBB opening in the rat for the subsequent progression of TLE. Albumin extravasation in human was prominent after status epilepticus (SE) in astrocytes and neurons, and also in hippocampus of TLE patients. Similarly, albumin and tracers were found in microglia, astrocytes and neurons of the rat. The BBB was permeable in rat limbic brain regions shortly after SE, but also in the latent and chronic epileptic phase. BBB permeability was positively correlated to seizure frequency in chronic epileptic rats. Artificial opening of the BBB by mannitol in the chronic epileptic phase induced a persistent increase in the number of seizures in the majority of rats. These findings indicate that BBB leakage occurs during epileptogenesis and the chronic epileptic phase and suggest that this can contribute to the progression of epilepsy.
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