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  • Pitts Burns posted an update 1 week, 5 days ago

    BACKGROUND Miscarriage is a prevalent public health issue and many events occur before women are aware of their pregnancy, complicating research design. Thus, risk factors for miscarriage are critically understudied. Fasiglifam purchase Our goal was to identify environmental chemicals with a high number of interactions with miscarriage genes, based on known toxicogenomic responses. METHODS We used miscarriage (MeSH D000022) and chemical gene lists from the Comparative Toxicogenomics Database in human, mouse, and rat. We assessed enrichment for gene ontology biological processes among the miscarriage genes. We prioritized chemicals (n = 25) found at Superfund sites or in the blood or urine pregnant women. For chemical-disease gene sets of sufficient size (n = 13 chemicals, n = 20 comparisons), chi-squared enrichment tests and proportional reporting ratios (PRR) were calculated. We cross-validated enrichment results. RESULTS Miscarriage was annotated with 121 genes and overrepresented in inflammatory response (q = 0.001), collagenscarriage, and thus linked to decreased probability of live birth, may limit the inclusion of fetuses susceptible to adverse birth outcomes in epidemiology studies. Our findings have critical public health implications for successful pregnancies and the interpretation of adverse impacts of environmental chemical exposures on pregnancy. The leafminer Liriomyza trifolii is an important insect pest of ornamental and vegetable crops worldwide. Temperature is a critical environmental factor that impacts both the distribution and interspecific competition of Liriomyza spp. In this study, we compared the transcriptomes of L. trifolii exposed to ambient (25 °C), hot (43 °C), and cold (-7 °C) temperatures. RNA-seq revealed 100,041 assembled unigenes, and 50,546 of these were annotated in L. trifolii transcriptome libraries. A total of 207 and 2904 differentially expressed genes (DEGs) were identified in response to hot and cold stress, respectively. Functional classification indicated that “cellular process”, “single organism processes” and “metabolic processes” pathways were significantly enriched, along with “binding activity” and “catalytic activity”. With respect to clusters of orthologous genes (COG) classification, DEGs were assigned to “post-translational modification, protein turnover, chaperones”, “carbohydrate transport and metabolism” and “lipid transport and metabolism” categories. Subsequent annotation and enrichment analyses indicated that genes encoding heat shock proteins (HSPs) and cuticular proteins were significantly up-regulated during heat and cold stress, respectively. This study expands our knowledge of gene expression in L. trifolii during temperature stress and provides a basis for further studies aimed at understanding the mechanism of thermotolerance in this important invasive leafminer fly. The pathophysiology of insomnia remains poorly understood, yet emerging cross-disciplinary approaches integrating natural history, observational studies in traditional populations, gene-phenotype expression and experiments are opening up new avenues to investigate the evolutionary origins of sleep disorders, with the potential to inform innovations in treatment. Previous authors have supported that acute insomnia is a normal biopsychosocial response to a perceived or real threat and may thus represent an adaptive response to stress. We further extend this hypothesis by claiming that insomnia reflects a fear-related evolutionary survival mechanism, which becomes persistent in some vulnerable individuals due to failure of the fear extinction function. Possible treatments targeting fear extinction are proposed, such as pharmacotherapy and emotion-based cognitive behavioral therapy. BACKGROUND Growing evidence suggests an independent relationship between habitual snoring and metabolic abnormalities. Currently, there are few data available on the association between snoring and hyperuricemia. Therefore, we evaluated the cross-sectional association between snoring and serum uric acid (UA) concentration and ascertain the effects of different snoring intensities on hyperuricemia among Chinese urban adults in Nanjing. METHODS We performed a cross-sectional study including 7699 participants (4197 men and 3502 women) from Nanjing Drum Tower Hospital aged ≥18 years over a two year (ie, 2016-2018) period. All participants were divided into four groups based on Snoring scores. Questionnaires, physical examinations and biochemical tests were conducted. Hyperuricemia was defined as levels of serum UA > 6.8 mg/dL in males and >6.0 mg/dL in females. We used a generalized linear model to investigate the association between snoring and serum UA concentration and logistic regression model to investigate nt hyperuricemia. VuLTP1.1, a LTP1 from Vigna unguiculata, inhibits 78.1 % of the human salivary α-amylase (HSA) activity at 20 μM. We had performed a correlation study between VuLTP1.1 structure and HSA inhibitory activity and showed that two VuLTP1.1 regions are responsible for HSA inhibition. In one of them we had characterized the crucial importance of an Arg39 for inhibition. In this work, we analyzed the VuLTP1.1-HSA interaction by protein-protein docking to understand the most probable interaction model and the mechanism of HSA inhibition by VuLTP1.1. The VuLTP1.1 tertiary structure quality and refinement as well as the docking assay between VuLTP1.1 and HSA were done by bioinformatic programs. HSA inhibition occurs by direct interaction of the VuLTP1.1 with the HSA causing the obstruction of the carbohydrate biding cleft with Gibbs free energy of -18.5 Kcal/mol and the dissociation constant of 2.6E-14 M. The previously identified Arg39 of VuLTP1.1 is burrowed into the active site of the HSA and there it interacts with the Asp300 of HSA catalytic site by a hydrogen bond. We had confirmed the importance of the Arg39 of VuLTP1.1 for the HSA inhibition which interacts with the Asp300 at the HSA active site. I-2, a LTP-like peptide, presents the same HSA inhibition pattern that VuLTP1.1, which indicates that the inhibition mechanism of the LTPs towards α-amylase is very similar. For the best of our knowledge, it is the first time that the HSA inhibition mechanism was understood and described for the LTP1s using VuLTP1.1 and I-2 as prototype inhibitors. A heterotrophic nitrifying-aerobic denitrifying bacterium isolated from deep-sea sediment was identified as Pseudomonas bauzanensis DN13-1. Nitrogen (N) removal capability and relative expression of nitrification and denitrification genes of this strain were investigated. The NO2–N, NO3–N and NH4+-N removal efficiencies were 98.82%, 65.87% and 98.89%, respectively, and strain DN13-1 could efficiently remove mixed N. Meanwhile, other inorganic N was not accumulated during these N removal processes. Genomic analysis indicated that genes nirS, norB, nosZ, nasA and putative amo were identified. The relative expression of functional genes by real-time PCR (qPCR) further confirmed nitrite, nitrate and ammonium removal pathways of strain DN13-1 under aerobic condition. Especially, the ammonium removal pathway of this strain was achieved through heterotrophic ammonium nitrification coupled with fast nitrite denitrification directly. Taken together, strain DN13-1 possesses particularity to efficiently remove N, which guarantees its promising application in aquaculture wastewater treatment. In spite of their various pharmacological properties the anti-inflammatory potential of benzo[c]phenanthridines remained underexplored. Thus, for the first time PDE4 inhibitory potential of 11,12-dihydro benzo[c]phenanthridine/benzo[c]phenanthridine was assessed in vitro. Elegant synthesis of these compounds was performed via a multi-step sequence consisting of a Pd-catalyzed unusual construction of 4-allyl isocoumarin ring and FeCl3-mediated intramolecular regio- as well as site-selective arene-allyl cyclization as key steps. The overall strategy involved Sonogashira coupling followed by isocoumarin and isoquinolone synthesis, then chlorination and subsequent cyclization to afford a range of 11,12-dihydro derivatives. One of these dihydro compounds was converted to the corresponding benzo[c]phenanthridine that showed concentration dependent inhibition of PDE4B affording an initial hit molecule. The SAR study suggested that 11,12-dihydro analogs were less potent than the compound having unsaturation at the same part of the ring. (±)-Petchilactones A-C (1-3), three pairs of enantiomeric meroterpenoids respectively with a 6/6/5/5 or a 5/5/5/7/6 ring system were isolated from Ganoderma petchii. Their structures including absolute configurations were assigned by using spectroscopic, computational, and X-ray diffraction methods. Compounds 1 and 2 represent a new skeletal meroterpenoid. Biological evaluation found that (-)-1 and (-)-3 could induce umbilical cord mesenchymal stem cells into keratinocyte-like cells. Three N-metallocenoylsphingosines with variance in the central metal (Fe, Co, Ru), the charge (neutral or cationic), and the arene ligands (Cp2, Cp*Ph) were synthesized from serine and metallocene carboxylic acids as substrate-analogous inhibitors of human acid ceramidase (AC). Their inhibitory potential was examined using the recombinant full length ASAH1 enzyme, expressed and secreted from High Five insect cells, and the fluorescent substrate Rbm14-12. All complexes inhibited AC, most strongly so ruthenium(II) complex 13a. Some antitumoral effects of the complexes, such as the interference with the microtubular and F-actin cytoskeleton of cancer cells, were correlated to their AC-inhibition, whereas others, e.g. their cytotoxicity and their induction of caspase-3/-7 activity in cancer cells, were not. All complexes accumulated preferentially in the lysosomes of cancer cells like their target AC, arrested the cells in G1 phase of the cell cycle, and displayed cytotoxicity with mostly single-digit micromolar IC50 values while inducing cancer cell apoptosis. Research in the domain of memory suggests that forgetting is primarily driven by interference and competition from other, related memories. Here we ask whether similar dynamics are at play in foreign language (FL) attrition. We tested whether interference from translation equivalents in other, more recently used languages causes subsequent retrieval failure in L3. In Experiment 1, we investigated whether interference from the native language (L1) and/or from another foreign language (L2) affected L3 vocabulary retention. On day 1, Dutch native speakers learned 40 new Spanish (L3) words. On day 2, they performed a number of retrieval tasks in either Dutch (L1) or English (L2) on half of these words, and then memory for all items was tested again in L3 Spanish. Recall in Spanish was slower and less complete for words that received interference than for words that did not. In naming speed, this effect was larger for L2 compared to L1 interference. Experiment 2 replicated the interference effect and asked if the language difference can be explained by frequency of use differences between native- and non-native languages. Overall, these findings suggest that competition from more recently used languages, and especially other foreign languages, is a driving force behind FL attrition.