Triterpenoids and Flavonoids from the Leaves of Astragalus membranaceus and Their Inhibitory Effects on Nitric Oxide Production

Four new cycloartane triterpenes, named huangqiyegenins V and VI and huangqiyenins K and L ( 1 – 4 , resp.), together with nine known triterpenoids, 5 – 13 , and eight flavonoids, 14 – 21 , were isolated from a 70%‐EtOH extract of Astragalus membranaceus leaves. The structures of the new compounds were elucidated by detailed spectroscopic analyses, and the compounds were identified as (9β,11α,16β,20R,24S)‐11,16,25‐trihydroxy‐20,24‐epoxy‐9,19‐cyclolanostane‐3,6‐dione ( 1 ), (9β,16β,24S)‐16,24,25‐trihydroxy‐9,19‐cyclolanostane‐3,6‐dione ( 2 ), (3β,6α,9β,16β,20R,24R)‐16,25‐dihydroxy‐3‐(β‐D ‐xylopyranosyloxy)‐20,24‐epoxy‐9,19‐cyclolanostan‐6‐yl acetate ( 3 ), and (3β,6α,9β,16β,24E)‐26‐(β‐D ‐glucopyranosyloxy)‐16‐hydroxy‐3‐(β‐D ‐xylopyranosyloxy)‐9,19‐cyclolanost‐24‐en‐6‐yl acetate ( 4 ). All isolated compounds were evaluated for their inhibitory activities against LPS‐induced NO production in RAW264.7 macrophage cells. Compounds 1 – 3, 14, 15 , and 18 exhibited strong inhibition on LPS‐induced NO release by macrophages with IC₅₀ values of 14.4–27.1 μM .     

Network-based Phenome-Genome Association Prediction by Bi-Random Walk

MotivationThe availability of ontologies and systematic documentations of phenotypes and their genetic associations has enabled large-scale network-based global analyses of the association between the complete collection of phenotypes (phenome) and genes. To provide a fundamental understanding of how the network information is relevant to phenotype-gene associations, we analyze the circular bigraphs (CBGs) in OMIM human disease phenotype-gene association network and MGI mouse phentoype-gene association network, and introduce a bi-random walk (BiRW) algorithm to capture the CBG patterns in the networks for unveiling human and mouse phenome-genome association. BiRW performs separate random walk simultaneously on gene interaction network and phenotype similarity network to explore gene paths and phenotype paths in CBGs of different sizes to summarize their associations as predictions.ResultsThe analysis of both OMIM and MGI associations revealed that majority of the phenotype-gene associations are covered by CBG patterns of small path lengths, and there is a clear correlation between the CBG coverage and the predictability of the phenotype-gene associations. In the experiments on recovering known associations in cross-validations on human disease phenotypes and mouse phenotypes, BiRW effectively improved prediction performance over the compared methods. The constructed global human disease phenome-genome association map also revealed interesting new predictions and phenotype-gene modules by disease classes.     

Hormonal regulation of uterine natural killer cells in mouse preimplantation uterus

Uterine Natural Killer (uNK) cells are the most abundant lymphocyte population recruited in the uteri during murine and human pregnancy. Previous investigation on uNK cells during mouse pregnancy focused more on its accumulation in postimplantation periods, which were believed to play important roles in regulating trophoblast invasion and angiogenesis towards successful placentation. However, by using recently developed methods of Dolichos biflorus agglutinin (DBA) lectin, a closer examination during mouse preimplantation revealed that there were also dynamic regulations of uNK cell, suggesting a major regulation by steroid hormones. Here we provide a detailed examination of uNK cells distribution during mouse early pregnancy by DBA lectin reactivity, with emphasis on preimplantation period and its hormonal regulation profiles. Our results showed that uNK precursor cells or its cell membrane specific components could be recruited in the uterus by estrogen or/and progesterone, and the effects could be completely abolished by specific antagonists of their nuclear receptors (estrogen and progesterone receptor). These results suggested that the preimplantation uterus, through concerted hormone regulation, could recruit uNK precursor cell or its specific cellular component, which might be conducive for uterine receptivity and further uNK construction/function during postimplantation.     

Mating behavior of the cabbage beetle, Colaphellus bowringi (Coleoptera: Chrysomelidae)

Abstract  Circadian mating rhythms, mating frequency, mating duration, and the effect of mating duration on fecundity and fertility in the cabbage beetle, Colaphellus bowringi were investigated in the laboratory. Mating occurred throughout the 24-h cycle but the majority of copulations occurred in the photophase with two apparent peaks, one at 8:00 and another at 16:00. Mating frequency observations for 10 consecutive days indicated that pre-mating period of C. bowringi was about 4 days, and pairs mated an average of 5 times per day and an average of 40 times during the first 10 days. There was a negative correlation between mating frequency and mating duration during the consecutive mating. The mean duration of the first copulation (136.24 ± 4.62 min) was significantly longer than those of the second (57.87 ± 2.03 min), third (53.05 ± 2.05 min) and fourth copulation (30.86 ± 2.98 min). Fecundity showed a slight increase with increasing mating duration but no significant difference among treatments. However, fertility was significantly influenced by the mating duration in this species. Mating of 20-min duration did not produce viable eggs. The mean percentage of fertile eggs with completed mating duration (204.43 ± 18.96 min, 56.75% fertile eggs) was significantly higher than those with 60 min (39.55%) and 30 min (17.91%) mating duration, suggesting that the longer mating duration might be associated with transfer of more sperm that are used to increase the fertility of eggs.     

The evolutionary impact of androgen levels on prostate cancer in a multi-scale mathematical model

Background  

Androgens bind to the androgen receptor (AR) in prostate cells and are essential survival factors for healthy prostate epithelium. Most untreated prostate cancers retain some dependence upon the AR and respond, at least transiently, to androgen ablation therapy. However, the relationship between endogenous androgen levels and cancer etiology is unclear. High levels of androgens have traditionally been viewed as driving abnormal proliferation leading to cancer, but it has also been suggested that low levels of androgen could induce selective pressure for abnormal cells. We formulate a mathematical model of androgen regulated prostate growth to study the effects of abnormal androgen levels on selection for pre-malignant phenotypes in early prostate cancer development.     

Synergistic actions between the SRP RNA and translating ribosome allow efficient delivery of the correct cargos during cotranslational protein targeting

During cotranslational protein targeting by the Signal Recognition Particle (SRP), the correct cargo accelerates stable complex assembly between the SRP and SRP receptor (FtsY) by several orders of magnitude, thus enabling rapid and faithful cargo delivery to the target membrane. The molecular mechanism underlying this cargo-induced rate acceleration has been unclear. Here we show that the SRP RNA allows assembly of the SRP-FtsY complex to be specifically stimulated by a correct cargo, and, reciprocally, a correct cargo enables the SRP RNA to optimize its electrostatic interactions with FtsY. These results combined with recent structural work led us to suggest a "conformational selection" model that explains the synergistic action of the SRP RNA with the cargo in accelerating complex assembly. In addition to its previously proposed role in preventing the premature dissociation of SRP and FtsY, we found that the SRP RNA also plays an active role in ensuring the formation of productive assembly intermediates, thus guiding the SRP and FtsY through the most efficient pathway of assembly.     

Effects of Water Stress on Chlorophyll-Protein Complexes in Wheat Chloroplasts

The excitation energy transfer from light harvesting chlorophyll protein complexes to PS Ⅱ was inhibited under water stress. The contents of iriternal antennae chlorophyll-protein complexes of PS Ⅱ (CPa), light harvesting chlorophyll-protein complexes of PS Ⅱ (LHC Ⅱ ), light harvesting chlorophyll-protein of PS Ⅰ (LHC Ⅰ ) and chlorophyll a protein complex of reaction center of PS Ⅰ were decreased by water stress. The decrease of chlorophyll-protein complexes of PS Ⅱ was greater than that of PS Ⅰ . It was indicated that the amount of 25 kD polypeptide of LHC Ⅱ in particular, as well as that of 43 and 47 kD polypeptides of CPa, and 21 kD polypeptide of LHC Ⅰ , were reduced by water stress.