Content determination of benzyl glucosinolate and anti–cancer activity of its hydrolysis product in Carica papaya L.

AbstractObjectiveTo determine the content of benzyl glucosinolate (BG) in the pulp and the seed and investigate the anti-cancer activity of its hydrolysis product in Carica papaya L.MethodsDetermination of BG was performed on an Hypersil BDS C18 column at the wavelength of 214 nm with 0.1% trifluoroacetic acid (TFA) aqueous solution (A) and 0.1%TFA acetonitrile (B) as the mobile phase. In vitro activity test was adopted with cultured human lung cancer H69 cell in vitro to investigate the inhibition rate of cell proliferation of benzyl isothiocyanate (BITC) against H69 cell.ResultsThe pulp has more BG before the maturation of papaya and it nearly disappeared after papaya matured, while the seed contains BG at every stage. Activity test demonstrated that the a higher concentration of BITC would have better inhibition rate of cell proliferation on H69 cell, and the IC50 was 6.5 μmol/L.ConclusionsBG also can be produced in the pulp of papaya and it will be stored in the seed after the fruit has been matured. The hydrolysis product of BG has certain cancer-prevention anti-cancer activities for human

Pathogen-origin horizontally transferred genes contribute to the evolution of Lepidopteran insects

<p>Abstract</p> <p>Background</p> <p>Horizontal gene transfer (HGT), a source of genetic variation, is generally considered to facilitate hosts' adaptability to environments. However, convincing evidence supporting the significant contribution of the transferred genes to the evolution of metazoan recipients is rare.</p> <p>Results</p> <p>In this study, based on sequence data accumulated to date, we used a unified method consisting of similarity search and phylogenetic analysis to detect horizontally transferred genes (HTGs) between prokaryotes and five insect species including <it>Drosophila melanogaster</it>, <it>Anopheles gambiae</it>, <it>Bombyx mori</it>, <it>Tribolium castaneum </it>and <it>Apis mellifera</it>. Unexpectedly, the candidate HTGs were not detected in <it>D. melanogaster</it>, <it>An. gambiae </it>and <it>T. castaneum</it>, and 79 genes in <it>Ap. mellifera </it>sieved by the same method were considered as contamination based on other information. Consequently, 14 types of 22 HTGs were detected only in the silkworm. Additionally, 13 types of the detected silkworm HTGs share homologous sequences in species of other Lepidopteran superfamilies, suggesting that the majority of these HTGs were derived from ancient transfer events before the radiation of Ditrysia clade. On the basis of phylogenetic topologies and BLAST search results, donor bacteria of these genes were inferred, respectively. At least half of the predicted donor organisms may be entomopathogenic bacteria. The predicted biochemical functions of these genes include four categories: glycosyl hydrolase family, oxidoreductase family, amino acid metabolism, and others.</p> <p>Conclusions</p> <p>The products of HTGs detected in this study may take part in comprehensive physiological metabolism. These genes potentially contributed to functional innovation and adaptability of Lepidopteran hosts in their ancient lineages associated with the diversification of angiosperms. Importantly, our results imply that pathogens may be advantageous to the subsistence and prosperity of hosts through effective HGT events at a large evolutionary scale.</p

DNMT3a in the hippocampal CA1 is crucial in the acquisition of morphine self‐administration in rats

Drug‐reinforced excessive operant responding is one fundamental feature of long-lasting addiction‐like behaviors and relapse in animals. However, the transcriptional regulatory mechanisms responsible for the persistent drug‐specific (not natural rewards) operant behavior are not entirely clear. In this study, we demonstrate a key role for one of the de novo DNA methyltransferase, DNMT3a, in the acquisition of morphine self‐administration (SA) in rats. The expression of DNMT3a in the hippocampal CA1 region but not in the nucleus accumbens shell was significantly up‐regulated after 1‐ and 7‐day morphine SA (0.3 mg/kg/infusion) but not after the yoked morphine injection. On the other hand, saccharin SA did not affect the expression of DNMT3a or DNMT3b. DNMT inhibitor 5‐aza‐2‐deoxycytidine (5‐aza) microinjected into the hippocampal CA1 significantly attenuated the acquisition of morphine SA. Knockdown of DNMT3a also impaired the ability to acquire the morphine SA. Overall, these findings suggest that DNMT3a in the hippocampus plays an important role in the acquisition of morphine SA and may be a valid target to prevent the development of morphine addiction. Includes Supplemental informatio

Merging Experts into One: Improving Computational Efficiency of Mixture of Experts

Scaling the size of language models usually leads to remarkable advancements in NLP tasks. But it often comes with a price of growing computational cost. Although a sparse Mixture of Experts (MoE) can reduce the cost by activating a small subset of parameters (e.g., one expert) for each input, its computation escalates significantly if increasing the number of activated experts, limiting its practical utility. Can we retain the advantages of adding more experts without substantially increasing the computational costs? In this paper, we first demonstrate the superiority of selecting multiple experts and then propose a computation-efficient approach called \textbf{\texttt{Merging Experts into One}} (MEO), which reduces the computation cost to that of a single expert. Extensive experiments show that MEO significantly improves computational efficiency, e.g., FLOPS drops from 72.0G of vanilla MoE to 28.6G (MEO). Moreover, we propose a token-level attention block that further enhances the efficiency and performance of token-level MEO, e.g., 83.3\% (MEO) vs. 82.6\% (vanilla MoE) average score on the GLUE benchmark. Our code will be released upon acceptance. Code will be released at: \url{https://github.com/Shwai-He/MEO}.Comment: EMNLP 2023 Main Conference (Oral

Targeted genetic analysis of cerebral blood flow imaging phenotypes implicates the INPP5D gene

The vascular hypothesis of Alzheimer's disease (AD) has proposed the involvement of brain hypoperfusion in AD pathogenesis, where cognitive decline and dysfunction result from dwindling cerebral blood flow (CBF). Based on the vascular hypothesis of Alzheimer's disease, we focused on exploring how genetic factors influence AD pathogenesis via the cerebrovascular system. To investigate the role of CBF endophenotypes in AD pathogenesis, we performed a targeted genetic analysis of 258 subjects from the Alzheimer's Disease Neuroimaging Initiative cohort to examine associations between 4033 single-nucleotide polymorphisms of 24 AD genes and CBF measures in 4 brain regions. A novel association with CBF measure in the left angular gyrus was identified in an INPP5D single-nucleotide polymorphism (i.e., rs61068452; p = 1.48E-7; corrected p = 2.39E-3). The gene-based analysis discovered both INPP5D and CD2AP associated with the left angular gyrus CBF. Further analyses on nonoverlapping samples revealed that rs61068452-G was associated with lower CSF t-tau/Aβ1–42 ratio. Our findings suggest a protective role of rs61068452-G in an AD-relevant cerebrovascular endophenotype, which has the potential to provide novel insights for better mechanistic understanding of AD

Burst expansion, distribution and diversification of MITEs in the silkworm genome

<p>Abstract</p> <p>Background</p> <p>Miniature inverted-repeat transposable elements (MITEs) are widespread in plants and animals. Although silkworm (<it>Bombyx mori</it>) has a large amount of and a variety of transposable elements, the genome-wide information of the silkworm MITEs is unknown.</p> <p>Results</p> <p>We used structure-based and homology approaches to search for MITEs in the silkworm genome. We identified 17 MITE families with a total of 5785 members, accounting for ~0.4% of the genome. 7 of 17 MITE families are completely novel based on the nucleotide composition of target site duplication (TSD) and/or terminal inverted repeats (TIR). Silkworm MITEs were widely and nonrandom distributed in the genome. One family named BmMITE-2 might experience a recent burst expansion. Network and diversity analyses for each family revealed different diversification patterns of the silkworm MITEs, reflecting the signatures of genome-shocks that silkworm experienced. Most silkworm MITEs preferentially inserted into or near genes and BmMITE-11 that encodes a germline-restricted small RNA might silence its the closest genes in silkworm ovary through a small RNA pathway.</p> <p>Conclusions</p> <p>Silkworm harbors 17 MITE families. The silkworm MITEs preferred to reside in or near genes and one MITE might be involved in gene silence. Our results emphasize the exceptional role of MITEs in transcriptional regulation of genes and have general implications to understand interaction between MITEs and their host genome.</p

A genome-wide association study identifies a genomic region for the polycerate phenotype in sheep (Ovis aries)

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