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Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New Zealand albino rabbits (n = 10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change three times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone. [ABSTRACT FROM AUTHOR]

Objectives This study was designed to evaluate the pharmacological activity and therapeutic mechanism of Xiaojin Pills (XJW) on lung cancer. Methods Mice were orally administered with Xiaojin Pills for 21 days. Tumour samples were collected to evaluate the antilung cancer effect, and blood samples were collected to identify differential metabolites with metabolomics. Through the analysis of network pharmacology, the active ingredients and targets related to XJW therapy for lung cancer were filtered. Key findings Different expression of seven metabolites related to seven pathways, including Arachidonic acid metabolism, Citrate cycle, tryptophan metabolism, glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, primary bile acid biosynthesis and nicotinate and nicotinamide metabolism, were demonstrated to explain the efficacy of XJW in the treatment of lung cancer. Furthermore, a total of 19 active ingredients (ursolic acid, α-thujone, pelargonidin, succinic acid, boswellic acid, muscone, daidzein, xanthorrhizol, isoeugenol, oleic acid, β-caryophyllene, vanillin, β-sitosterol, lupeol, palmitic acid, eugenol, methylbutenol, β-elemene and quercetin) acted directly on 9 targets (CAT, PTGS2, PTGS1, CTH, ABTA, ALT1, ME2, AGXT and AGXT 2) and regulated 3 out of 7 metabolites (3-Hydroxyanthranilic acid, Pyruvate and Prostaglandin G2). Conclusions Through metabolomics and network pharmacology analyses, this study demonstrated that the major metabolites of XJW in treating lung cancer were regulated by multitarget and multicomponent interaction network. [ABSTRACT FROM AUTHOR]

Context: While fibrosis in endometriosis has recently loomed prominently, the sources of myofibroblasts, the principal effector cell in fibrotic diseases, remain largely obscure. Mesothelial cells (MCs) can be converted into myofibroblasts through mesothelial-mesenchymal transition (MMT) in many fibrotic diseases and adhesion.Objective: To evaluate whether MCs contribute to the progression and fibrogenesis in endometriosis through MMT.Setting, Design, Patients, Intervention, and Main Outcome Measures: Dual immunofluorescence staining and immunohistochemistry using antibodies against calretinin, Wilms' tumor-1 (WT-1), and α-smooth muscle actin (α-SMA) were performed on lesion samples from 30 patients each with ovarian endometrioma (OE) and deep endometriosis (DE), and 30 normal endometrial (NE) tissue samples. Human pleural and peritoneal MCs were co-cultured with activated platelets or control medium with and without neutralization of transforming growth factor β1 (TGF-β1) and/or platelet-derived growth factor receptor (PDGFR) and their morphology, proliferation, and expression levels of genes and proteins known to be involved in MMT were evaluated, along with their migratory and invasive propensity, contractility, and collagen production.Results: The number of calretinin/WT-1 and α-SMA dual-positive fibroblasts in OE/DE lesions was significantly higher than NE samples. The extent of lesional fibrosis correlated positively with the lesional α-SMA staining levels. Human MCs co-cultured with activated platelets acquire a morphology suggestive of MMT, concomitant with increased proliferation, loss of calretinin expression, and marked increase in expression of mesenchymal markers. These changes coincided with functional differentiation as reflected by increased migratory and invasive capacity, contractility, and collagen production. Neutralization of TGF-β1 and PDGFR signaling abolished platelet-induced MMT in MCs.Conclusions: MCs contribute to lesional progression and fibrosis through platelet-induced MMT. [ABSTRACT FROM AUTHOR]

Motivation The main function of protein – RNA interaction is to regulate the expression of genes. Therefore, studying protein – RNA interactions is of great significance. The information of three-dimensional (3D) structures reveals that atomic interactions are particularly important. The calculation method for modeling a 3D structure of a complex mainly includes two strategies: free docking and template-based docking. These two methods are complementary in protein – protein docking. Therefore, integrating these two methods may improve the prediction accuracy. Results In this article, we compare the difference between the free docking and the template-based algorithm. Then we show the complementarity of these two methods. Based on the analysis of the calculation results, the transition point is confirmed and used to integrate two docking algorithms to develop P3DOCK. P3DOCK holds the advantages of both algorithms. The results of the three docking benchmarks show that P3DOCK is better than those two non-hybrid docking algorithms. The success rate of P3DOCK is also higher (3 – 20%) than state-of-the-art hybrid and non-hybrid methods. Finally, the hierarchical clustering algorithm is utilized to cluster the P3DOCK's decoys. The clustering algorithm improves the success rate of P3DOCK. For ease of use, we provide a P3DOCK webserver, which can be accessed at www.rnabinding.com/P3DOCK/P3DOCK.html. An integrated protein – RNA docking benchmark can be downloaded from http://rnabinding.com/P3DOCK/benchmark.html. Availability and implementation www.rnabinding.com/P3DOCK/P3DOCK.html. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background Infections are common and can be fatal in patients undergoing long-term dialysis. Recent studies have shown conflicting evidence associating infection with vitamin D status or use of vitamin D and have not been systematically reviewed in this population. Methods We searched PubMed, Web of Science, Cochrane Library, Embase and three Chinese databases from inception until December 2017 for interventional [non-randomized or randomized controlled trials (RCTs)], cohort and case–control studies on levels of serum 25-hydroxyvitamin D [25(OH)D] or use of vitamin D [supplemental nutritional vitamin D or vitamin D receptor activator (VDRA)] and infection (any infection, infection-required hospitalization or infection-related death or composite) in long-term dialysis patients. We conducted a meta-analysis on the relative risk (RR) of infection and level of 25(OH)D or use of vitamin D. Results Of 2440 reports identified, 17 studies met inclusion criteria, all with moderate quality, with 6 cohort studies evaluating 25(OH)D serum concentrations (n  = 5714) and 11 (2 RCTs and 9 observational studies) evaluating the use of vitamin D (n  = 92 309). The risk of composite infection was 39% lower {relative risk [RR] 0.61 [95% confidence interval (CI) 0.41–0.89]} in the subjects with high or normal levels of 25(OH)D than in those with low levels. When compared with those who did not use vitamin D, the pooled adjusted risk for composite infection was 41% lower in those who used vitamin D [RR 0.59 (95% CI 0.43–0.81)]. Conclusions High or normal serum levels of 25(OH)D and the use of vitamin D, particularly VDRA, were each associated with a lower risk of composite infection in long-term dialysis patients. [ABSTRACT FROM AUTHOR]

Clinical pharmacogenomics (PGx) has the potential to make pharmacotherapy safer and more effective by utilizing genetic patient data for drug dosing and selection. However, widespread adoption of PGx depends on its successful integration into routine clinical care through clinical decision support tools, which is often hampered by insufficient or fragmented infrastructures. This paper describes the setup and implementation of a unique multimodal, multilingual clinical decision support intervention consisting of digital, paper-, and mobile-based tools that are deployed across implementation sites in seven European countries participating in the Ubiquitous PGx (U-PGx) project. [ABSTRACT FROM AUTHOR]

Sesquiterpenes are one of the most important defensive secondary metabolite components of agarwood. Agarwood, which is a product of the Aquilaria sinensis response to external damage, is a fragrant and resinous wood that is widely used in traditional medicines, incense and perfume. We previously reported that jasmonic acid (JA) plays an important role in promoting agarwood sesquiterpene biosynthesis and induces expression of the sesquiterpene synthase ASS1, which is a key enzyme that is responsible for the biosynthesis of agarwood sesquiterpenes in A. sinensis. However, little is known about this molecular regulation mechanism. Here, we characterized a basic helix-loop-helix transcription factor, AsMYC2, from A. sinensis as an activator of ASS1 expression. AsMYC2 is an immediate-early jasmonate-responsive gene and is co-induced with ASS1. Using a combination of yeast one-hybrid assays and chromatin immunoprecipitation analyses, we showed that AsMYC2 bound the promoter of ASS1 containing a G-box motif. AsMYC2 activated expression of ASS1 in tobacco epidermis cells and up-regulated expression of sesquiterpene synthase genes (TPS21 and TPS11) in Arabidopsis, which was also promoted by methyl jasmonate. Our results suggest that AsMYC2 participates in the regulation of agarwood sesquiterpene biosynthesis in A. sinensis by controlling the expression of ASS1 through the JA signaling pathway. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate burn-related variations of inflammation and immunity. Fifty-five mice were divided randomly into sham burn and burn groups. Eighty-seven hospitalized burn patients were also reviewed. In mice, neutrophils and monocytes were elevated significantly on post burn day (PBD 1). Lymphocytes were reduced on PBDs 1 and 3. Levels of serum tumor necrosis factor-α and interleukin-6 were highest on PBD 1. Interleukin-1β levels were the highest on PBD 3. On PBD 3, CD4CD25T regulatory cells/CD4 cells in spleen were higher. On PBDs 1, 3, 7, and 14, percentage of splenic dendritic cells were significantly lower than the sham burn group. In patients, neutrophils and monocytes were significantly elevated on PBD 1. Levels declined but remained elevated at most days to PBD 7. Lymphocytes in burn groups 1 and 2 were reduced on PBDs 1 and 3, respectively. Our results exhibited that severe burn injury initiated a hyperinflammatory response and immunosuppression. PBDs 1 to 3 were important for changes in inflammation and immunosuppression. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the efficiency of corticosteroid, leflunomide and mesenchymal stem cells (MSCs) in the treatment of pediatric idiopathic pulmonary hemosiderosis (IPH). Methods: Ten patients were included in the study. The diagnosis of IPH was based on clinical symptoms, laboratory examinations and pulmonary hemosiderosis. Induction therapy consisted of methylprednisolone pulse therapy, followed by prednisone plus leflunomide. Maintenance therapy consisted of low-dose prednisone, leflunomide and administration of MSCs. Results: All the patients achieved complete response after treatment with corticosteroid, leflunomide and MSCs. The median follow-up was 23 months (range: 4-34 months). Moreover, administration of MSCs induced an increase in the percentage of CD4+ CD25+ regulatory T cells but a decrease in the percentage of Th17 cells. Conclusion: Treatment with corticosteroid, leflunomide and MSCs for pediatric IPH was safe and effective. [ABSTRACT FROM AUTHOR]

Anthocyanins are major pigments in plants. Methylation plays a role in the diversity and stability of anthocyanins. However, the contribution of anthocyanin methylation to lower coloration is still unclear. We identified two homologous anthocyanin O-methyltransferase (AOMT) genes from purple-lowered (PsAOMT) and red-lowered (PtAOMT) Paeonia plants, and we performed functional analyses of the two genes in vitro and in vivo. The critical amino acids for AOMT catalytic activity were studied by site-directed mutagenesis. We showed that the recombinant proteins, PsAOMT and PtAOMT, had identical substrate preferences towards anthocyanins. The methylation activity of PsAOMT was 60 times higher than that of PtAOMT in vitro. Interestingly, this vast difference in catalytic activity appeared to result from a single amino acid residue substitution at position 87 (arginine to leucine). There were significant differences between the 35S::PsAOMT transgenic tobacco and control lowers in relation to their chromatic parameters, which further confirmed the function of PsAOMT in vivo. The expression levels of the two homologous AOMT genes were consistent with anthocyanin accumulation in petals. We conclude that AOMTs are responsible for the methylation of cyanidin glycosides in Paeonia plants and play an important role in purple coloration in Paeonia spp. [ABSTRACT FROM AUTHOR]

Background: Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. Methods: This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). Results: UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73m²) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 newcases of non-dipperwere identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of nondiabetics and in participants with normal range UAER. Conclusions: UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations. [ABSTRACT FROM AUTHOR]

Cellular patterning in the Arabidopsis (Arabidopsis thaliana) root epidermis is dependent on positional information, the transmission of which involves histone acetylation. Here, we report that HISTONE DEACETYLASE6 (HDA6) has significant effects on this cellular patterning. Mutation of HDA6 led to ectopic hair cells in the nonhair positions of root epidermis in Arabidopsis, based on an analysis of paraffin sections stained with Toluidine Blue. While HDA6 was present throughout the root tip, epidermis-specific complementation with HDA6 could rescue the hda6 phenotype. Both transcript levels and expression patterns of ENHANCER OF TRIPTYCHON AND CAPRICE1 (ETC1) and GLABRA2 (GL2) in the root tip were affected in hda6. Consistent with these changes in expression, HDA6 directly bound to the promoter regions of ETC1 and GL2, and acetylation of histone H3 on these promoter regions and acetylation of histone H4 on the ETC1 promoter region was increased in the hda6 mutant. Taken together, these results indicate that HDA6 affects the cellular patterning of Arabidopsis root epidermis through altering the histone acetylation status of ETC1 and GL2 promoters and thereby affects the expression of these two components of the core transcription factor network determining epidermal cell fates. Our findings thus provide new insights into the role of histone acetylation in root epidermis cell patterning. [ABSTRACT FROM AUTHOR]

Abscisic acid (ABA) plays an essential role in seed germination. In this study, we demonstrate that one SNF1-RELATED PROTEIN KINASE3-type protein kinase, SOS2-LIKE PROTEIN KINASE5 (PKS5), is involved in ABA signal transduction via the phosphorylation of an interacting protein, ABSCISIC ACID-INSENSITIVE5 (ABI5). We found that pks5-3 and pks5-4, two previously identified PKS5 superactive kinase mutants with point mutations in the PKS5 FISL/NAF (a conserved peptide that is necessary for interaction with SOS3 or SOS3-LIKE CALCIUM BINDING PROTEINs) motif and the kinase domain, respectively, are hypersensitive to ABA during seed germination. PKS5 was found to interact with ABI5 in yeast (Saccharomyces cerevisiae), and this interaction was further confirmed in planta using bimolecular fluorescence complementation. Genetic studies revealed that ABI5 is epistatic to PKS5. PKS5 phosphorylates a serine (Ser) residue at position 42 in ABI5 and regulates ABA-responsive gene expression. This phosphorylation was induced by ABA in vivo and transactivated ABI5. Expression of ABI5, in which Ser-42 was mutated to alanine, could not fully rescue the ABA-insensitive phenotypes of the abi5-8 and pks5-4abi5-8 mutants. In contrast, mutating Ser-42 to aspartate rescued the ABA insensitivity of these mutants. These data demonstrate that PKS5-mediated phosphorylation of ABI5 at Ser-42 is critical for the ABA regulation of seed germination and gene expression in Arabidopsis (Arabidopsis thaliana). [ABSTRACT FROM AUTHOR]

In China, the woolly apple aphid, Eriosoma lanigerum (Hausmann), was first detected as an invasive species during the 1910s to 1930s, restricted to Shandong, Liaoning, and Yunnan Provinces. However, since the 1990s, the pest has spread into many other areas of China. To determine the possible spread routes of the recently established populations, the genetic diversity and genetic structure of 24 populations in 10 provinces were analyzed using eight microsatellite loci. Analyses using STRUCTURE software identified two genetic clusters overall. Three populations from Yunnan and Xinjiang consisted of individuals originating from a single cluster. Nineteen populations from eight northern provinces consisted only of individuals from another cluster, which formed a single large and panmictic population, resembling a distinct "supercolony" in Northern China. The other two populations from Yunnan consisted of individuals from both clusters. The possible routes of spread of the recently established populations of E. lanigerum in China were revealed as follows: 1) the populations in Northern China (including these from Henan, Hebei, Shanxi, Shannxi, Jiangsu, and Gansu) may have been introduced from Shandong or Liaoning Provinces; 2) the populations in Yunnan consisted of an early-established population and a population introduced secondarily from Shandong or neighboring areas, indicating that the population in Yunnan has at least two sources; and 3) the recently established populations of E. lanigerum in Xinjiang might not have been introduced from the "supercolony" in Northern China. Knowledge of these routes of spread is useful for avoiding further dissemination and/or additional introductions. [ABSTRACT FROM AUTHOR]

Serum-free cultures of insect cells play an important role in the fields of protein engineering, medicine, and biology. In this paper, the suspension cell line QB-Tn9-4s of Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae) was successfully adapted to serum-free Sf-900 III medium and passaged for 52 generations. The adapted QB-Tn9-4s cells grew faster. Their population doubling time shortened from 27.4 hr in serum-containing medium to 24.1 hr, and their maximal density increased by 1.83-fold, reaching 3.50 × 106 cells/mL in serum-free culture in T-flasks. The cells readily adapted to spinner culture, with maximum cell density of 4.40 × 106 cells/mL in a spinner flask. Although the infection rate of Autographa californica multiple nucleopolyhedrovirus and production of occlusion bodies (OBs) of the adapted QB-Tn9-4s cells were 91.0% and 85.4 OBs/cell, respectively, similar to those of QB-Tn9-4s cells cultured in serum-containing medium and control BTI-Tn5B1-4 cells, their budded virus titer was 4.97 × 107 TCID50/mL, significantly higher than those of the latter two. In addition, the expression levels of ß-galactosidase at six days post-infection and secreted alkaline phosphatase at seven days postinfection in the adapted QB-Tn9-4s cells reached 2.98 ± 0.15×104 IU/mL and 3.34 ± 0.13 IU/mL, respectively, significantly higher than those of QB-Tn9-4s and control BTI-Tn5B1-4 cultured in serum-containing media. The above findings establish a foundation for industrial production of virus and recombinant proteins in QB-Tn9-4s serum-free culture. [ABSTRACT FROM AUTHOR]

The present study investigated the biochemical composition, including the amino acids and fatty acids profiles of the ovaries and hepatopancreas of the female marine crab, Charybdis japonica (A. Milne-Edwards, 1861), at different physiological stages (immature, mature, spawning and abortion), together with the dynamic changes of the Gonadosomatic Index (GSI) and Hepatosomatic Index (HSI) during gonad development. A significant inverse relationship between GSI and HSI (R = -0.82; P < 0.05) was recorded. The protein, total amino-acid (TAA), essential amino acid (EAA) and polyunsaturated fatty acid (PUFA) content and the ratio of n-3/n-6 in the ovaries were significantly higher than those in the hepatopancreas, while the content of moisture and saturated fatty acid (SFA) were lower. From immature to mature, the content of proteins and lipids in ovaries increased, and the content of carbohydrates decreased noticeably, while these tendencies in hepatopancreas were in the reverse order. A significant increase in the total amount of TAA and EAA in ovaries of mature stages was measured; the content of all amino acids increased, except for arginine, which decreased slightly. The content of PUFA in the ovaries increased with maturation, while the content of monounsaturated fatty acid (MUFA) decreased. Abundant threonine, methionine, leucine and C22:6n-3 (docosahexaenoic acid, DHA) were observed in the hepatopancreas of spawning crabs. Compared to spawning crabs, the content of protein and ash in the hepatopancreas of aborting crabs decreased significantly, while the carbohydrates content rose, and that the content of TAA, EAA and PUFA in the ovaries and hepatopancreas of aborting crabs were all lower, especially the amount of n-3 fatty acids in hepatopancreas, which decreased substantially, including DHA from 9.02% to 3.25%, and eicosapentaenoic acid (EPA) from 0.93% to 0.44%. [ABSTRACT FROM AUTHOR]

Chemical characteristics of normal, woolly apple aphid-damaged, and mechanically damaged twigs of six apple cultivars: Red Fuji, Golden Delicious, Qinguan, Zhaojinl08, Starkrimson, and Red General, were examined in autumn wood to provide a better understanding of factors related to cultivar resistance to the woolly apple aphid, Eriosoma lanigerum (Hausmann). Chemical measures examined included soluble sugars, soluble proteins and amino acids, total phenolics, and polyphenol oxidase (that enhances the resistance of plants to insects) and superoxide dismutase, peroxidase, and catalase (that degrade waste products in plants). Soluble sugar, protein, and amino acid contents in normal (undamaged) twigs of Red Fuji, aphid-susceptible cultivar, were higher than in mechanically damaged and aphid-damaged twigs. Total phenolic compounds, an important group of defensive compounds against aphids, increased by 30.5 and 6.0% in mechanically damaged twigs of Qinguan and Zhaojinl08, respectively, and decreased by 21.7 and 16.1% in aphid-damaged twigs of Red Fuji and Red General, respectively. Compared with normal twigs, in aphid-damaged twigs, superoxide dis-mutase, peroxidase, and polyphenol activity all decreased in Red Fuji. The resistance of some apple cultivars to woolly apple aphid during the growth of autumn shoots was related to several of the physiological indices we monitored. The thin epidermis of callus tissue over healed wounds showed increased susceptibility to the attack by woolly apple aphid. Apple cultivar Qinguan with the highest level of resistance to woolly apple aphid in autumn had increased in amino acid, total phenolic compound levels, and enzyme activity after aphid feeding. [ABSTRACT FROM AUTHOR]

Background: Although nerve fibres are present in eutopic and ectopic endometrium, it is unclear whether they appear in ovarian endometriotic lesions. We investigated the presence of nerve fibres in ovarian endometriotic lesions and its correlation with clinical parameters in women with ovarian endometriosis.Methods: Histological sections of ovarian endometriotic lesions from 61 women with ovarian endometriosis (Stages II-IV) who underwent laparoscopic endometrioma cystectomy were stained immunohistochemically using a specific polyclonal rabbit anti-protein gene product 9.5 (PGP9.5) antibody to demonstrate myelinated and unmyelinated nerve fibres.Results: Nerve fibres stained with PGP9.5 were detected in ovarian endometriotic lesions in 31.1% of women, and most appeared in fibrotic interstitium of ovarian endometriotic lesions. The density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions in women with pain symptoms (n = 35) was higher than in women with no pain symptoms (n = 26, P = 0.039), although the percentage (positive cases/total) of PGP9.5-positive fibres did not differ. In women with pain symptoms, PGP9.5-positive fibres appeared in 40.0% of cases and the density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions was correlated with severity of pain symptoms (r = 0.466, P = 0.005). In women with no pain, PGP9.5-positive fibres were detected in only 5 (19.2%) women. Both the percentage and the density of PGP9.5-positive fibres in ovarian endometriotic lesions were associated with pelvic adhesions (chi2 = 6.833, P = 0.009; Z = 2.442, P = 0.015, respectively) but not with disease severity.Conclusions: PGP9.5-immunoactive nerve fibres in ovarian endometriotic lesions may be involved in the pathophysiology of pain generation and pelvic adhesion formation in women with ovarian endometriosis. [ABSTRACT FROM AUTHOR]

Sugar transporters are central machineries to mediate cross-membrane transport of sugars into the cells, and sugar availability may serve as a signal to regulate the sugar transporters. However, the mechanisms of sugar transport regulation by signal sugar availability remain unclear in plant and animal cells. Here, we report that a sucrose transporter, MdSUT1, and a sorbitol transporter, MdSOT6, both localized to plasma membrane, were identified from apple (Malus damestica) fruit. Using a combination of the split-ubiquitin yeast two-hybrid, immunocoprecipitation, and bimolecular fluorescence complementation assays, the two distinct sugar transporters were shown to interact physically with an apple endoplasmic reticulum-anchored cytochrome b5 MdCYB5 in vitro and in vivo. In the yeast systems, the two different interaction complexes function to upregulate the affinity of the sugar transporters, allowing cells to adapt to sugar starvation. An Arabidopsis (Arabidopsis thaliana) homolog of MdCYB5, AtCYB5-A, also interacts with the two sugar transporters and functions similarly. The point mutations leucine-73 → proline in MdSUT1 and leucine-117 → proline in MdSOT6, disrupting the bimolecular interactions but without significantly affecting the transporter activities, abolish the stimulating effects of the sugar transporter-cytochrome b5 complex on the affinity of the sugar transporters. However, the yeast (Saccharomyces cerevisiae) cytochrome b5 ScCYB5, an additional interacting partner of the two plant sugar transporters, has no function in the regulation of the sugar transporters, indicating that the observed biological functions in the yeast systems are specific to plant cytochrome b5s. These findings suggest a novel mechanism by which the plant cells tailor sugar uptake to the surrounding sugar availability. [ABSTRACT FROM AUTHOR]

NAD+-dependent sorbitol dehydrogenase (NAD-SDH, EC 1.1.1.14), a key enzyme in sorbitol metabolism, plays an important role in regulating sink strength and determining the quality of apple fruit. Understanding the tissue and subcellular localization of NAD-SDH is helpful for understanding sorbitol metabolism in the apple. In this study, two NAD-SDH cDNA sequences were isolated from apple fruits (Malus domestica Borkh cv. Starkrimson) and named MdSDH5 and MdSDH6. Immunohistochemical analysis revealed that NAD-SDH is distributed in both the flesh and the vascular tissue of the fruit, and the vascular tissue and mesophyll tissue in the young and old leaves, indicating that it is a ubiquitous protein expressed in both sink and source organs. Immunogold electron microscopy analysis demonstrated that NAD-SDH is localized mainly in the cytoplasm and chloroplast of the fruit and leaves. The chloroplast localization of NAD-SDH was confirmed by the transient expression of MdSDH5-GFP and MdSDH6-GFP in the mesophyll protoplast of Arabidopsis. NAD-SDH was also found in electron opaque deposits of vacuoles in young and mature leaves. These data show that NAD-SDH has different subcellular localizations in fruit and leaves, indicating that it might play a different role in sorbitol metabolism in different tissues of apple. [ABSTRACT FROM PUBLISHER]

Comparative analyses of the sequence of entire genomes have shown that gene duplications, chromosomal segmental duplications, or even whole genome duplications (WGD) have played prominent roles in the evolution of many eukaryotic species. Here, we used the ancient duplication of a well known transcription factor in maize, encoded by the Opaque-2 (O2) locus, to examine the general features of divergences of chromosomal segmental duplications in a lineage-specific manner. We took advantage of contiguous chromosomal sequence information in rice (Oryza sativa, Nipponbare), sorghum (Sorghum bicolor, Btx623), and maize (Zea mays, B73) that were aligned by conserved gene order (synteny). This analysis showed that the maize O2 locus is contained within a 1.25 million base-pair (Mb) segment on chromosome 7, which was duplicated ≈56 million years ago (mya) before the split of rice and maize 50 mya. The duplicated region on chromosome 1 is only half the size and contains the maize OHP gene, which does not restore the o2 mutation although it encodes a protein with the same DNA and protein binding properties in endosperm. The segmental duplication is not only found in rice, but also in sorghum, which split from maize 11.9 mya. A detailed analysis of the duplicated regions provided examples for complex rearrangements including deletions, duplications, conversions, inversions, and translocations. Furthermore, the rice and sorghum genomes appeared to be more stable than the maize genome, probably because maize underwent allotetraploidization and then diploidization. [ABSTRACT FROM PUBLISHER]

Many biochemical approaches show functions of calcium-dependent protein kinases (CDPKs) in abscisic acid (ABA) signal transduction, but molecular genetic evidence linking defined CDPK genes with ABA-regulated biological functions at the whole-plant level has been lacking. Here, we report that ABA stimulated two homologous CDPKs in Arabidopsis thaliana, CPK4 and CPK11. Loss-of-function mutations of CPK4 and CPK11 resulted in pleiotropic ABA-insensitive phenotypes in seed germination, seedling growth, and stomatal movement and led to salt insensitivity in seed germination and decreased tolerance of seedlings to salt stress. Double mutants of the two CDPK genes had stronger ABA- and salt-responsive phenotypes than the single mutants. CPK4- or CPK11-overexpressing plants generally showed inverse ABA-related phenotypes relative to those of the loss-of-function mutants. Expression levels of many ABA-responsive genes were altered in the loss-of-function mutants and overexpression lines. The CPK4 and CPK11 kinases both phosphorylated two ABA- responsive transcription factors, ABF1 and ABF4, in vitro, suggesting that the two kinases may regulate ABA signaling through these transcription factors. These data provide in planta genetic evidence for the involvement of CDPK/calcium in ABA signaling at the whole-plant level and show that CPK4 and CPK11 are two important positive regulators in CDPK/calcium-mediated ABA signaling pathways. [ABSTRACT FROM AUTHOR]

Sister-chromatid cohesion, the process of pairing replicated chromosomes during mitosis and meiosis, is mediated through the essential cohesin complex and a number of nonessential cohesion genes, hut the specific roles of these nonessential genes in sister-chromatid cohesion remain to be clarified. We analyzed sister-chromatid cohesion in double mutants of rnrc1Δ, tof1Δ, and csm3Δ and identified additive cohesion defects that indicated the existence of at least two pathways that contribute to sister-chromatid cohesion. To understand the relationship of other nonessential cohesion genes with respect to these two pathways, pairwise combinations of deletion and temperature-sensitive alleles were tested for cohesion defects. These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1. Furthermore, we found that the nonessential genes are not important for the maintenance of cohesion at G2/M. Thus, our data suggest that nonessential cohesion genes make critical redundant contributions to the establishment of sister-chromatid cohesion and define two cohesion pathways, thereby establishing a framework for understanding the role of nonessential genes in sister-chromatid cohesion. [ABSTRACT FROM AUTHOR]

In Deinococcus radiodurans, RecBCD holoenzyme is not intact because of the absence of RecB and RecC, but a RecD-like protein does indeed exist. In this work, D. radiodurans recD disruptant was constructed and its possible biological functions were investigated. The results showed that disruption of the recD gene of D. radiodurans resulted in a remarkably increased sensitivity to hydrogen peroxide but had no apparent effect on the resistance to γ and UV radiation. Furthermore, complementation experiments showed that Escherichia coli RecD, helicase domain or N-terminal domain of D. radiodurans RecD could not individually restore the resistant phenotype to hydrogen peroxide of the recD disruptant, whereas the complete D. radiodurans RecD protein could. Further studies showed that D. radiodurans RecD took part in antioxidant process by stimulating catalase activity and reactive oxygen species scavenging activity in D. radiodurans. These results suggest that D. radiodurans RecD has a new role in the antioxidant pathway. [ABSTRACT FROM AUTHOR]

Background Adult obesity is a well-established risk factor for endometrial cancer. However, little is known about the association of endometrial cancer risk with body size early in life and weight change during adulthood. We investigated whether women with greater early-age body size or with greater weight change during adulthood have an increased risk of endometrial cancer.Methods We analysed data from a population-based case–control study of endometrial cancer conducted between 1997 and 2001 in Shanghai, China. Included in this analysis were 832 endometrial cancer cases aged 30–69 years and 846 population controls. Information on weight and height history from adolescence through adulthood was obtained via structured in-person interviews. A logistic regression model was used to derive odds ratios (ORs) and 95% confidence intervals (CIs) for endometrial cancer in association with adolescent and adult adiposity, as well as adult body weight change. All ORs were adjusted for age, education, menstrual status, duration of menstruation, number of pregnancies, oral contraceptive use, and family history of cancer.Results Perceived weights and heights during puberty that were greater than average were associated with a modestly increased risk of cancer. The association for perceived weight was substantially weakened after adjustment for current body mass index (BMI). High BMI at all adult ages significantly predicted endometrial cancer risk, with recent BMI being the strongest predictor. Further analyses disclosed that weight gain during adulthood, particularly during the peri-menopausal period (age 40–50 years), was associated with a significantly elevated risk of endometrial cancer, even among currently non-obese women. Gaining >5 kg between age 40 and 50 was related to ORs of 2.3 (95% CI 1.4–3.9) for women with a BMI < 25 kg/m2 and 2.0 (95% CI 1.3–3.0) for women with BMI ≥ 25 kg/m2.Conclusions Adult weight gain, particularly during the peri-menopausal period, plays a significant role in the development of endometrial cancer risk. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol signaling pathway and the relevant metabolites are known to be critical to the modulation of different aspects of plant growth, development, and stress responses. Inositol polyphosphate 5-phosphatase is a key enzyme involved in phosphatidylinositol metabolism and is encoded by an At5PTase gene family in Arabidopsis thaliana. A previous study shows that At5PTase11 mediates cotyledon vascular development probably through the regulation of intracellular calcium levels. In this study, we provide evidence that At5PTase13 modulates the development of cotyledon veins through its regulation of auxin homeostasis. A T-DNA insertional knockout mutant, At5pt13-1, showed a defect in development of the cotyledon vain, which was rescued completely by exogenous auxin and in part by brassinolide, a steroid hormone. Furthermore, the mutant had reduced auxin content and altered auxin accumulation in seedlings revealed by the DR5:β-glucuronidase fusion construct in seedlings. In addition, microarray analysis shows that the transcription of key genes responsible for auxin biosynthesis and transport was altered in At5pt13-1. The At5pt13-1 mutant was also less sensitive to auxin inhibition of root elongation. These results suggest that At5PTase13 regulates the homeostasis of auxin, a key hormone controlling vascular development in plants. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are important plant growth regulators in multiple developmental processes. Previous studies have indicated that BR treatment enhanced auxin-related responses, but the underlying mechanisms remain unknown. Using 14C-labeled indole-3-acetic acid and Arabidopsis thaliana plants harboring an auxin-responsive reporter construct, we show that the BR brassinolide (BL) stimulates polar auxin transport capacities and modifies the distribution of endogenous auxin. In plants treated with BL or defective in BR biosynthesis or signaling, the transcription of PIN genes, which facilitate functional auxin transport in plants, was differentially regulated. In addition, BL enhanced plant tropistic responses by promoting the accumulation of the PIN2 protein from the root tip to the elongation zone and stimulating the expression and dispersed localization of ROP2 during tropistic responses. Constitutive overexpression of ROP2 results in enhanced polar accumulation of PIN2 protein in the root elongation region and increased gravitropism, which is significantly affected by latrunculin B, an inhibitor of F-actin assembly. The ROP2 dominant negative mutants (35S-ROP2-DA/DN) show delayed tropistic responses, and this delay cannot be reversed by BL addition, strongly supporting the idea that ROP2 modulates the functional localization of PIN2 through regulation of the assembly/reassembly of F-actins, thereby mediating the BR effects on polar auxin transport and tropistic responses. [ABSTRACT FROM AUTHOR]

The authors conducted a population-based case-control study of 832 endometrial cancer cases and 846 frequency-matched controls in Shanghai, China (1997–2001), to examine the association of overall adiposity and body fat distribution with disease risk. Overall adiposity was estimated using weight and body mass index (BMI); upper body fat distribution was evaluated using waist circumference and waist:hip ratio. Overall and upper-body obesity were both associated with an elevated risk of endometrial cancer. Adjusted odds ratios and 95% confidence intervals for highest-versus-lowest quartile comparisons were 2.6 (95% confidence interval (CI): 2.0, 3.5) for weight, 2.9 (95% CI: 2.2, 3.9) for BMI, 4.7 (95% CI: 3.4, 6.4) for waist circumference, and 3.5 (95% CI: 2.6, 4.8) for waist:hip ratio. The positive associations with weight and BMI vanished after results were controlled for waist circumference, while associations with waist circumference and waist:hip ratio persisted after adjustment for BMI. The positive association with upper-body obesity was more pronounced among younger women, women who had never used oral contraceptives, and women with a history of diabetes mellitus (p for multiplicative interaction < 0.05). Upper-body obesity was related to increased risk among women with low BMI. These results suggest that obesity, particularly upper-body fat deposition, is associated with an increased risk of endometrial cancer. [ABSTRACT FROM AUTHOR]

Investigates strain and age-related changes in the localization of intestinal CD161+ natural killer cells and CD8+ intraepithelial lymphocytes along the longitudinal crypt axis in inbred rats. Differences in the growth parameters among the inbred rat strains; Important role that CD161+ natural killer cells appear to play in immune-surveillance at the bottom of intestinal crypts.

A putative Membrane Steroid Binding Protein (designated MSBP1) was identified and functionally characterized as a negative regulator of cell elongation in Arabidopsis thaliana. The MSBP1 gone encodes a 220-amino acid protein that can bind to progesterone, 5-dihydrotestosterone, 24-epi-brassinolide (24-eBL), and stigmasterol with different affinities in vitro. Transgenic plants overexpressing MSBP1 showed short hypocotyl phenotype and increased steroid binding capacity in membrane fractions, whereas antisense MSBP1 transgenic plants showed long hypocotyl phenotypes and reduced steroid binding capacity, indicating that MSBP1 negatively regulates hypocotyl elongation. The reduced cell elongation of MSBP1-overexpressing plants was correlated with altered expression of genes involved in cell elongation, such as expansins and extensins, indicating that enhanced MSBP1 affected a regulatory pathway for cell elongation. Suppression or over-expression of MSBP1 resulted in enhanced or reduced sensitivities, respectively, to exogenous progesterone and 24-eBL, suggesting a negative role of MSBP1 in steroid signaling. Expression of MSBP1 in hypocotyls is suppressed by darkness and activated by light, suggesting that MSBP1, as a negative regulator of cell elongation, plays a role in plant photomorphogenesis. This study demonstrates the functional roles of a steroid binding protein in growth regulation in higher plants. [ABSTRACT FROM AUTHOR]

Inositol polyphosphates, such as inositol trisphosphate, are pivotal intracellular signaling molecules in eukaryotic cells. In higher plants the mechanism for the regulation of the type and the level of these signaling molecules is poorly understood. In this study we investigate the physiological function of an Arabidopsis (Arabidopsis thaliana) gene encoding inositol polyphosphate kinase (AtIPK2α), which phosphorylates inositol 1,4,5-trisphosphate successively at the D-6 and D-3 positions, and inositol 1,3,4,5-tetrakisphosphate at D-6, resulting in the generation of inositol 1,3,4,5,6-pentakisphosphate. Semiquantitative reverse transcription-PCR and promoter-β-glucuronidase reporter gene analyses showed that AtIPK2α is expressed in various tissues, including roots and root hairs, stem, leaf, pollen grains, pollen tubes, the flower stigma, and siliques. Transgenic Arabidopsis plants expressing the AtIPK2α antisense gene under its own promoter were generated. Analysis of several independent transformants exhibiting strong reduction in AtIPK2α transcript levels showed that both pollen germination and pollen, tube growth were enhanced in the antisense lines compared to wild-type plants, especially in the presence of nonoptimal low Ca2+ concentrations m the culture medium. Furthermore, root growth and root hair development were also stimulated in the antisense lines, in the presence of elevated external Ca2+ concentration or upon the addition of EGTA. In addition, seed germination and early seedling growth was stimulated in the antisense lines. These observations suggest a general and important role of AtIPK2α, and hence inositol polyphosphate metabolism, in the regulation of plant growth most likely through the regulation of calcium signaling, consistent with the well-known function of inositol trisphosphate in the mobilization of intracellular calcium stores. [ABSTRACT FROM AUTHOR]

A novel SET‐domain‐containing gene OsSET1 was isolated from rice (Oryza sativa L.). Its deduced protein consists of 895 amino acids. OsSET1 has a high degree of structure similarity to other SET‐domain‐containing genes such as CLF in higher plants and E(z) in animals. RT‐PCR showed that the gene expresses throughout the entire plant. A transient expression assay in onion epidermis revealed that the OsSET1 protein is localized in nuclei. Over‐expression of the SET domain of OsSET1 in Arabidopsis resulted in altered shoot development at seedling stages. [ABSTRACT FROM PUBLISHER]

Certain polyphenols inhibit the activity of aromatase, a critical enzyme in estrogen synthesis that is coded by the CYP19A1 gene. Consumption of polyphenol-rich foods and beverages, thus, may interact with CYP19A1 genetic polymorphisms in the development of endometrial cancer. The authors tested this hypothesis in the Shanghai Endometrial Cancer Study (1997–2003), a population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls. Dietary information was obtained by use of a validated food frequency questionnaire. Genotypes of CYP19A1 at rs28566535, rs1065779, rs752760, rs700519, and rs1870050 were available for 1,042 cases and 1,035 controls. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals after adjustment for potential confounding factors. Higher intake of soy foods and tea consumption were both inversely associated with the risk of endometrial cancer, with odds ratios of 0.8 (95% confidence interval: 0.6, 1.0) for the highest versus the lowest tertiles of intake of soy and 0.8 (95% confidence interval: 06, 0.9) for ever tea consumption. The association of single nucleotide polymorphisms rs1065779, rs752760, and rs1870050 with endometrial cancer was modified by tea consumption (pinteraction CYP19A1 genetic polymorphisms on the development of endometrial cancer. [ABSTRACT FROM AUTHOR]

TRIMs (terminal-repeat retrotransposons in miniature), which are characterized by their small size, have been discovered in all investigated vascular plants and even in animals. Here, we identified a highly conservative TRIM family referred to as Wukong elements in the maize genome. The Wukong family shows a distinct pattern of tandem arrangement in the maize genome suggesting a high rate of unequal crossing over. Estimation of insertion times implies a burst of retrotransposition activity of the Wukong family after the allotetraploidization of maize. Using next-generation sequencing data, we detected 87 new Wukong insertions in parents of the maize NAM population relative to the B73 reference genome and found abundant insertion polymorphism of Wukong elements in 75 re-sequenced maize lines, including teosinte, landraces, and improved lines. These results suggest that Wukong elements possessed a persistent retrotransposition activity throughout maize evolution. Moreover, the phylogenetic relationships among 76 maize inbreds and their relatives based on insertion polymorphisms of Wukong elements should provide us with reliable molecular markers for biodiversity and genetics studies. [ABSTRACT FROM AUTHOR]