The Influences of A Nitrogen Atom Position in Dinucleoside 2-,3-,4-Pyridylphosphonates on Fragmentation Patterns in Electrospray Ionization Multistage Tandem Mass Spectra

2-,3-,4-Pyridylphosphonates and their phosphonothioate congeners were analyzed by electrospray ionization multistage tandem mass spectrometry (ESI-MSⁿ). It was found that the fragmentation pathways of these compounds were not influenced to any detectable extent by the stereochemistry at the phosphorus centers but were sensitive to the position of a nitrogen atom in the pyridine ring of these compounds. Possible mechanisms for fragmentations of the investigated compounds are discussed in detail.

     

Simple Synthesis and Anti-Hiv Activity of Novel 3′-Vinyl Branched Apiosyl Pyrimidine Nucleosides

Novel vinyl branched apiosyl nucleosides were synthesized in this study. Apiosyl sugar moiety was constructed by sequential ozonolysis and reductions. The bases (uracil and thymine) were efficiently coupled by glycosyl condensation procedure (persilyated base and TMSOTf). The antiviral activities of the synthesized compounds were evaluated against the HIV-1, HSV-1, HSV-2, and HCMV. Compound 10β displayed moderate anti-HIV activity (EC₅₀ = 17.3 μg/mL) without exhibiting any cytotoxicity up to 100 μM.     

piRNA-Triggered MIWI Ubiquitination and Removal by APC/C in Late Spermatogenesis

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Highlights? MIWI is a substrate of APC/C, and piRNA loading is essential for MIWI ubiquitination ? piRNA loading promotes MIWI binding to the APC/C substrate-binding subunit ? MIWI and piRNAs are coordinately eliminated in late spermatids ? Inhibition of MIWI destruction in late spermatids prevents sperm maturation     

Enhanced Phase II Detoxification Contributes to Beneficial Effects of Dietary Restriction as Revealed by Multi-platform Metabolomics Studies

Dietary restriction (DR) has many beneficial effects, but the detailed metabolic mechanism remains largely unresolved. As diet is essentially related to metabolism, we investigated the metabolite profiles of urines from control and DR animals using NMR and LC/MS metabolomic approaches. Multivariate analysis presented distinctive metabolic profiles and marker signals from glucuronide and glycine conjugation pathways in the DR group. Broad profiling of the urine phase II metabolites with neutral loss scanning showed that levels of glucuronide and glycine conjugation metabolites were generally higher in the DR group. The up-regulation of phase II detoxification in the DR group was confirmed by mRNA and protein expression levels of uridinediphospho-glucuronosyltransferase and glycine-N-acyltransferase in actual liver tissues. Histopathology and serum biochemistry showed that DR was correlated with the beneficial effects of low levels of serum alanine transaminase and glycogen granules in liver. In addition, the Nuclear factor (erythroid-derived 2)-like 2 signaling pathway was shown to be up-regulated, providing a mechanistic clue regarding the enhanced phase II detoxification in liver tissue. Taken together, our metabolomic and biochemical studies provide a possible metabolic perspective for understanding the complex mechanism underlying the beneficial effects of DR.It has been known for more than 70 years that dietary restriction (DR)¹ can extend the life span and delay the onset of age-related diseases, based on an early rodent study showing such effects (1). However, not until the 1980s was DR recognized as a good model for studying the mechanism of or inhibitory measures for aging (2). So far, extensive studies employing model organisms such as yeasts, nematodes, fruit flies, and rodents have shown that DR has beneficial effects in most of the species studied (for a review, see Ref. 3). Most notably, a recent 20-year-long study showed that monkeys, the species closest to humans, also benefit from DR similarly (4). Although there has not been (or could not have been) a systematic study on the effects of DR on the human life span, several longitudinal studies strongly suggest that changes in dietary intake can affect the life span and/or disease-associated marker values greatly (5–7).This inverse correlation between dietary intake and long-term health strongly indicates that DR''s effects should involve metabolism, and that DR elicits the reorganization of metabolic pathways. It also seems quite natural that something we eat should affect the body''s metabolism. Despite this seemingly straightforward relationship between diet and metabolism, the mechanisms underlying the beneficial effects of DR are anything but simple. Intensive efforts, spanning decades, to understand the mechanisms of DR have identified several genes that might mediate the effects of DR, such as mTOR, IGF-1, AMPK, and SIRT1 (for a review, see Ref. 8). Still, most of them are involved in early nutrient-sensing steps, and specific metabolic pathways, especially those at the final steps actually responsible for the effects of DR, are largely unknown.This might be at least partially due to the fact that previous studies have focused mostly on genomic or proteomic changes induced by DR, instead of looking at changes in metabolism or metabolites directly. Metabolomics, which has gained much interest in recent years (9–11), might be a good alternative for addressing the mechanistic uncertainty of DR''s effects, with the direct profiling of metabolic changes elicited by environmental factors. In contrast to genomics or proteomics, which often employ DNA or proteins extracted from particular tissues, metabolomics studies mostly employ body fluids (i.e. urine or blood), which can reflect the metabolic status of multiple organs, enabling investigations at a more systemic level. In particular, urine has been used extensively to study the mechanism of external stimuli (i.e. drugs or toxic insults) at most major target organs, such as the lung, kidney, liver, or heart (12–18). Still, metabolomics studies of DR effects have been very limited. A few previous ones reported the changes in phenomenological urine metabolic markers with DR, without identification and/or validation of specific metabolic pathways reflected at the actual tissue or enzyme level (19, 20). Therefore, those studies fell short of providing a mechanistic perspective on DR''s effects. In addition, they employed either NMR or LC/MS approaches without validation across the two analytical platforms.Among the metabolic pathways that can directly affect the integrity of multiple organs, and hence long-term health, are phase II detoxification pathways (21). Typically, lipophilic endo/xenobiotics are metabolized first by a phase I system, such as cytochrome P450, which modifies the compounds so that they have hydrophilic functional groups for increased solubility. In many cases, though, these modifications might increase the reactivity of the compounds, leading to cellular damage. The phase II detoxification systems involve conjugation reactions that attach charged hydrophilic molecular moieties to reactive metabolites, thus facilitating the elimination of the harmful metabolites from body, ultimately reducing their toxicity (22). These systems are thus especially important in protecting cellular macromolecules, such as DNA and proteins, from reactive electrophilic or nucleophilic metabolites. The enzymes involved in these processes include glutathione-S-transferase (GST), sulfotransferase, glycine-N-acyltransferase (GLYAT), and uridinediphospho-glucuronosyltransferase (UGT), with the last enzyme being the most prevalent (23). The beneficial effects of phase II reactions have been particularly studied in relation to the mechanism of healthy dietary ingredients. It is well believed that many such foods can prevent cancers (hence the term “chemoprevention”) by inducing phase II detoxification systems (24–26). Although DR also substantially reduces the incidence of cancers, the exact mechanism remains elusive.Here, we employed multi-platform metabolomics to obtain metabolic perspectives on the beneficial effects of DR on rats. Our results about urine metabolomics markers suggest that DR enhances the phase II detoxification pathway, which was confirmed by means of conjugation metabolite profiling and changes in mRNA/protein expression levels of phase II enzymes in actual liver tissues. A possible molecular mechanism was also addressed through the exploration of Nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) pathway activation upon DR. We believe the current study provides new metabolic insights into DR''s beneficial effects, as well as a workflow for studying DR''s effects from a metabolic perspective.     

Changes of butterfly communities after forest fire

Fires change the diversity and composition of insects in forest ecosystems. In the present study, we examined the change of butterfly communities after a fire including the increase of butterfly richness, grassland species, and generalist species, and more changed communities. Butterflies were surveyed for 5 years after the big Uljin fire in 2007. During each year, butterflies were counted monthly by the line transect method from April to October at two sites (burned vs. unburned, ~ 1.5 km routes). Specialist grassland species decreased in the year of the fire but generalist species did not increase significantly. Butterfly richness did not change but butterfly diversity decreased due to a sudden increase of a species, Polygonia c-aureum. The butterfly community in the year of the fire was different from those in later years, showing temporary change of community in the year of the fire. Species composition was significantly different between burned and unburned sites, but this phenomenon cannot be interpreted as an influence of fire due to highly variable species composition of local butterfly assemblages and the non-repetitive sampling site of the present study.     

Tailoring immunoglobulin Fc for highly potent and serum-stable therapeutic antibodies

Antibody Fc region, a recruiter and a frontline commander in the combat against cancer and infectious pathogens, mediates potent immune effector functions by engaging Fc receptors and serum complement proteins. Recent studies indicate that the Fc region is particularly amenable to modifications that enhance potency and serum stability through amino acid substitution and glycan modification. In order to modulate the interaction of the Fc domain with Fc-binding ligands (FcγRs, C1q, and FcRn), various engineering strategies have been employed; these studies are discussed in this review.     

Fumigant toxicity of Apiaceae essential oils and their constituents against Sitophilus oryzae and their acetylcholinesterase inhibitory activity

We evaluated the insecticidal and acetylcholinesterase (AChE) inhibition activities of the essential oils and their constituents of 10 Apiaceae on the adult rice weevil, Sitophilus oryzae. Of the 10 species tested, dill (Anethum graveolens), caraway (Carum carvi), and cumin (Cuminum cyminum) essential oils showed strong fumigant toxicity against adult S. oryzae. LC₅₀ values of caraway, dill, and cumin essential oils were 2.45, 3.29, and 4.75 mg/L air, respectively. Among the test compounds, (+)-carvone, (?)-carvone, cuminaldehyde, dihydrocarvone, linalool oxide, carveol, trans-anethole, and neral demonstrated strong fumigant toxicity against adult S. oryzae with LC₅₀ values of 0.61, 0.84, 1.12, 2.92, 3.76, 4.29, 5.02, and 6.60 mg/L air, respectively. α-Pinene showed the strongest AChE inhibition activity followed by β-pinene and limonene. The measured toxicity of the artificial blends of the constituents identified in dill and cumin oils indicated that (+)-carvone and cuminaldehyde were major contributors to the fumigant toxicity of the artificial blend.     

Female sex pheromone components of the box tree pyralid,Glyphodes perspectalis,in Korea: Field test and development of film-type lure

The box tree pyralid, Glyphodes perspectalis, is the most destructive pest of the box tree in Korea and was recently introduced into Europe. The previously known as EAG active components of this moth, (Z)-11-hexadecenal (Z11-16:Ald), (E)-11-hexadecenal (E11-16:Ald), and (Z)-11-hexadecenol (Z11-16:OH) have been detected from the extracts of female abdomen. The ratios of these three compounds identified in female moth were 5.2:1:0.2 in 2010 and 6.5:1:0.2 in 2011. During field bioassays, it was found that the male moths were not attracted to Z11-16:Ald or E11-16:Ald when used alone; however, they were attracted to a mixture of the above. The most effective ratios of Z11-16:Ald to E11-16:Ald were 5:1 and 7:1. A small amount of Z11-16:OH inhibited male moth attraction in field bioassays. Further, a uni-trap was found to be more effective in catching the moth than delta and wing traps were. In field bioassays using 2 different types of lures, significantly more male G. perspectalis were caught to film-type lures (50.5 ± 4.4/trap) than those to rubber septum lures (35.8 ± 5.2/trap).     

Flower model traps reduced thrips infestations on a pepper crop in field

A flower model trap developed by modifying an artificial yellow chrysanthemum flower was more attractive to flower thrips than commercial yellow sticky traps. Installation of these flower model traps (20 traps per 50 m² plot) was reported to reduce seasonal populations of Frankliniella intonsa (Trybom) (Thysanoptera: Thripidae) on strawberry flowers in greenhouses. In this study, we sought to determine if the installation of such flower model traps would reduce thrips populations in a pepper field. The traps were installed at the bottom of the plant canopy at varying densities (0, 5, 10, and 20 traps) in 20 plots (each 3 × 5 m²) using a completely randomized design. Thrips populations on pepper flowers were sampled from 1 to 29 July in 2009. All thrips sampled on the flowers were identified as F. intonsa. A significant effect of treatment and sampling date was found from repeated-measure analysis of variance. The highest density (20 traps per 15 m²) of traps significantly reduced the female and male F. intonsa population compared to the control by 61 and 49%, respectively. However, no difference in immature thrips numbers was found among the treatments. These results indicate that this flower model trap can be a useful tool for the management of flower thrips on field-grown peppers.