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Genome characterization of California poppy (Eschscholzia californica cv. "Hitoezaki"), which produces pharmaceutically important benzylisoquinoline alkaloids (BIAs), was carried out using the draft genome sequence. The numbers of tRNA and rRNA genes were close to those of the other plant species tested, whereas the frequency of repetitive sequences was distinct from those species. Comparison of the predicted genes with those of Amborella trichopoda, Nelumbo nucifera, Solanum lycopersicum, and Arabidopsis thaliana, and analyses of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway indicated that the enzyme genes involved in BIA biosynthesis were highly enriched in the California poppy genome. Further comparative analysis using the genome information of Papaver somniferum and Aquilegia coerulea, both BIA-producing plants, revealed that many genes encoding BIA biosynthetic enzymes, transcription factors, transporters, and candidate proteins, possibly related to BIA biosynthesis, were specifically distributed in these plant species.The RNA polymerase (RNAP) clamp, a mobile structural element conserved in RNAP from all domains of life, has been proposed to play critical roles at different stages of transcription. In previous work, we demonstrated using single-molecule Förster resonance energy transfer (smFRET) that RNAP clamp interconvert between three short-lived conformational states (lifetimes ∼ 0.3-0.6 s), that the clamp can be locked into any one of these states by small molecules, and that the clamp stays closed during initial transcription and elongation. Here, we extend these studies to obtain a comprehensive understanding of clamp dynamics under conditions RNAP may encounter in living cells. We find that the RNAP clamp can populate long-lived conformational states (lifetimes > 1.0 s) and can switch between these long-lived states and the previously observed short-lived states. In addition, we find that clamp motions are increased in the presence of molecular crowding, are unchanged in the presence of elevated monovalent-cation concentrations, and are reduced in the presence of elevated divalent-cation concentrations. Finally, we find that RNAP bound to non-specific DNA predominantly exhibits a closed clamp conformation. Our results raise the possibility of additional regulatory checkpoints that could affect clamp dynamics and consequently could affect transcription and transcriptional regulation.Nucleosome-nucleosome interactions drive the folding of nucleosomal arrays into dense chromatin fibers. A better physical account of the folding of chromatin fibers is necessary to understand the role of chromatin in regulating DNA transactions. Here, we studied the unfolding pathway of regular chromatin fibers as a function of single base pair increments in linker length, using both rigid base-pair Monte Carlo simulations and single-molecule force spectroscopy. Both computational and experimental results reveal a periodic variation of the folding energies due to the limited flexibility of the linker DNA. We show that twist is more restrictive for nucleosome stacking than bend, and find the most stable stacking interactions for linker lengths of multiples of 10 bp. We analyzed nucleosomes stacking in both 1- and 2-start topologies and show that stacking preferences are determined by the length of the linker DNA. Moreover, we present evidence that the sequence of the linker DNA also modulates nucleosome stacking and that the effect of the deletion of the H4 tail depends on the linker length. Importantly, these results imply that nucleosome positioning in vivo not only affects the phasing of nucleosomes relative to DNA but also directs the higher-order structure of chromatin.

To examine the effect of alcohol cue exposure on tobacco-related cravings, self-administration and other measures of tobacco-related cue reactivity.

We searched Medline, PsycINFO, Embase, CINAHL and Scopus from inception to May 2020 for articles reporting on a combination of cue reactivity (and/or cross-cue reactivity), alcohol use and tobacco consumption. A semi-quantitative analysis and study quality assessment were performed for the included articles.

A total of 37 articles met our inclusion criteria and were included in the systematic review. Most studies (60%) reported that alcohol cue exposure increased tobacco cravings, but only 18% of studies reported that alcohol cue exposure resulted in an increase in ad libitum smoking. There was also substantial heterogeneity between studies due to differences in methodology related to alcohol cue exposure, measures of tobacco cravings, as well as variable participant and study characteristics.

Alcohol cue exposure can increase cravings for tobacco. This has important implications for individuals who use both substances but are trying to quit one or both.

Alcohol cue exposure can increase cravings for tobacco. This has important implications for individuals who use both substances but are trying to quit one or both.To investigate the modulation of endogenous indole-3-acetic acid (IAA) level by biosynthesis and inactivation during floral development, IAA and its metabolites were analyzed by LC-ESI/MS/MS in Lychee (Litchi chinensis Sonn.) flowers. In the bloomed flowers, the level of free IAA was higher in males than in females. In contrast, the total sum level of IAA metabolites was higher in females than in males, suggesting a higher biosynthetic activity of IAA in the females before the bloom. A detailed time-course analysis from the bud stage to the developing flower stage showed higher levels of IAA in females than males. The major metabolites were oxidized IAA in both sexes. The results suggest that IAA is involved in the maturation of female floral tissues in lychee, and oxidative metabolism plays an essential role in controlling the free IAA levels therein.Gangliosides (GLSs) are ubiquitously distributed in all tissues but highly enriched in nervous system. Currently, it is unclear how exogenous GLSs regulate neuritogenesis, although neural functions of endogenous GLSs are widely studied. Herein, we evaluated the neuritogenic activities and mechanism of sea urchin gangliosides (SU-GLSs) in vitro. These different glycosylated SU-GLSs, including GM4(1S), GD4(1S), GD4(2A), and GD4(2G), promoted differentiation of NGF-induced PC12 cells in a dose-dependent and structure-selective manner. Sulfate-type and disialo-type GLSs exhibited stronger neuritogenic effects than monosialoganglioside GM1. Furthermore, SU-GLSs might act as neurotrophic factors possessing neuritogenic effects, via targeting tyrosine-kinase receptors (TrkA and TrkB) and activating MEK1/2-ERK1/2-CREB and PI3K-Akt-CREB pathways. This activation resulted in increased expression and secretion of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). These pathways were verified by specific inhibitors. Our results confirmed the neuritogenic functions of SU-GLS in vitro and indicated their potential roles as natural nutrition for neuritogenesis.The Asian traditional medicinal plant Acorus calamus and its component α-asarone exhibited various biological activities, such as antiinflammation and antioxidant effects. In the present study, we investigated the in vitro effects of A. calamus extract and α-asarone on oxidative stress- and endoplasmic reticulum (ER) stress-induced cell death in hippocampal HT22 cells. A. calamus extract and α-asarone both significantly suppressed cell death induced by the oxidative stress inducer l-glutamate and ER stress inducer tunicamycin. A. calamus extract and α-asarone also significantly reduced reactive oxygen species (ROS) production induced by l-glutamate. Moreover, A. calamus extract and α-asarone suppressed the phosphorylation of protein kinase RNA-like ER kinase (PERK) induced by tunicamycin. These results suggest that A. calamus extract and α-asarone protect hippocampal cells from oxidative stress and ER stress by decreasing ROS production and suppressing PERK signaling, respectively. α-Asarone has potential as a potent therapeutic candidate for neurodegenerative diseases, including Alzheimer's disease.The long-term imposition of pressure overload on the cardiac tissue causes left ventricular hypertrophy (LVH) and cardiac fibrosis. Pinitol has been reported to possess antioxidant potential. The aim was to evaluate the efficacy of pinitol against pressure overload-induced cardiac hypertrophy and fibrosis in the aortic stenosis (AS) rat model. Cardiac hypertrophy was produced in Sprague-Dawley rats by abdominal aortic constriction and treated with lisinopril (15 mg/kg) or pinitol (5, 10, and 20 mg/kg). Pressure overload-induced alterations in hemodynamic and left ventricular function tests, cardiac SOD, GSH, MDA, NO, Na-K-ATPase, and mitochondrial complex enzyme levels were significantly attenuated by pinitol. The upregulated mRNA expressions of cardiac ANP, BNP, cTn-I, TNF-α, IL-1β, IL-6, Bax, Caspase-3, collagen-I, and cardiac apoptosis were markedly downregulated by pinitol. In conclusion, pinitol ameliorated pressure overload-induced LVH and fibrosis via its anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic potential in experimental AS.Leveraging the state of absorbed moisture within a polymer network to identify physical and chemical features of the host material is predicated upon a clear understanding of the interaction between the polymer and a penetrant water molecule; an understanding that has remained elusive. Recent work has revealed that a novel damage detection method that exploits the very low baseline levels of water typically found in polymer matrix composites (PMC) may be a valuable tool in the composite NDE arsenal, provided that a clear understanding of polymer-water interaction can be obtained. Precise detection, location, and possible quantification of the extent of damage can be performed by characterizing the physical and chemical states of moisture present in an in-service PMC. Composite structures have a locally elevated dielectric constant near the damage sites due to a higher fraction of bulk ("free") water, which has a higher dielectric constant when compared to water molecules bound to the polymer network through secondary bonding interactions. In this study, we aim to get a clear atomistic scale picture of the interactions which drive the dielectric signature variations necessary for tracking damage. Molecular Dynamics (MD) simulations were used to explore the effect of temperature on the state of moisture in two epoxy matrices with identical chemical constituents but different morphologies. The motivation was to understand whether higher polarity binds a greater fraction of moisture even at higher temperatures, leading to suppressed dielectric activity. Consequently, the influence of secondary bonding interactions was investigated to understand the impact of temperature on the absorbed water molecules in a composite epoxy matrix.Previously, the 5 kDa retentate (5kDaR) of a casein hydrolysate (CH) and yeast β-glucan (YBG) were identified as promising anti-inflammatory dietary supplements for supporting intestinal health in pigs post-weaning. However, their direct effects on intestinal bacterial populations are less well-known. The main objectives of this study were to determine if the increasing concentrations of the CH, 5kDaR and YBG individually, can (1) alter the bacterial and short-chain fatty acid profiles in a weaned pig faecal batch fermentation assay, and (2) directly influence the growth of selected beneficial (Lactobacillus plantarum, L. reuteri, Bifidobacterium thermophilum) and pathogenic (Enterotoxigenic Escherichia coli, Salmonella Typhimurium) bacterial strains in individual pure culture growth assays. The potential of CH as a comparable 5kDaR substitute was also evaluated. The 5kDaR increased lactobacilli counts and butyrate concentration in the batch fermentation assay (P less then 0.05) and increased L. plantarum (linear, P less then 0.

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