Background and aims

Pollination-induced floral changes, which have been widely documented in flowering plants, have been assumed to enhance the plant's reproductive success. However, our understanding of the causes and consequences of these changes is still limited. Using an alpine gynodioecious species, Cyananthus delavayi, we investigated the factors affecting floral closure and estimated the fitness consequences of floral closure.

Methods

The timings of floral closure and fertilization were determined. The effects of pollen load, pollen type (cross- or self-pollen) and floral morph (female or perfect flower) on the occurrence of floral closure were examined. Ovule fertilization and seed production were examined to investigate the causes and consequences of floral closure. Flowers were manipulated to prevent closing to detect potential benefits for female fitness.

Key Results

Floral closure, which could be induced by a very low pollen load, occurred within 4–7 h after pollination, immediately following fertilization. The proportion of closed flowers was influenced by pollen load and floral morph, but not by pollen type. Floral closure was more likely to occur in flowers with a higher proportion of fertilized ovules, but there was no significant difference in seed production between closed and open flowers. Those flowers in which closure was induced by natural pollination had low fruit set and seed production. Additionally, seed production was not influenced by closing-prevented manipulation when sufficient pollen deposition was received.

Conclusions

The occurrence of floral closure may be determined by the proportion of fertilized ovules, but this response can be too sensitive to ensure sufficient pollen deposition and can, to some extent, lead to a cost in female fitness. These results implied that the control of floral receptivity by the recipient flowers does not lead to an optimal fitness gain in C. delavayi.

Objectives

To validate the role of high mobility group box-1(HMGB1) in diagnosis of acute appendicitis (AA) with different pathological severity.

Methods

According to the pathologically diagnosis, 150 patients underwent appendectomies between Jan. 2007 and Dec, 2010 were divided into acute simple, acute suppurative and acute gangrenous appendicitis as group 1, 2 and 3, respectively. Each patient group contains 50 sex and age matched cases to make comparison with 50 healthy volunteers. The mRNA and protein expression levels of serum HMGB1 were determined by real-time quantitative PCR and enzyme linked immunosorbent assay (ELISA). Serum High-sensitivity C-reactive protein (hs-CRP) levels were determined by rate nephelometric immunoassay.

Results

In comparison with health volunteers, relative HMGB1 mRNA levels in group 1, 2 and 3 were significantly increased 3.05 ± 0.51,8.33 ± 0.75 and 13.74 ± 1.09 folds, reflecting a tendency of augmented severity. In accordance, serum protein levels of HMGB1 were 10.97 ± 1.64, 14.42 ± 1.56 and 18.08 ± 2.41 ng/ml in 3 patient groups, which are significantly higher than that of healthy volunteers’ 5.47 ± 0.73 ng/ml. hs-CRP levels were 12.85 ± 3.41, 21.04 ± 1.98 and 31.07 ± 5.46 ng/ml in 3 patients groups compared with 2.06 ± 0.77 ng/ml in controls. The concentrations of HMGB1 and hs-CRP were both positively correlated with disease severity.

Conclusion

Serum HMGB1 constitutes as a valuable marker in diagnosis of AA. Positively correlated with hs-CRP level, mRNA and protein expression of HMGB1 to a certain extent reflected the severity of AA.

Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging. The GdSL was prepared using synthesized Gd(III)-DOTA-1,2-distearoyl-sn-glycero-3-phosphoethanolamine lipid. Sonosensitivity of GdSL to 20-kHz ultrasound induced 33% to 40% of DOX release. The relaxivities (r1) of GdSL were 6.6 to 7.8 mM−1 s−1, which were higher than that of MR-bester®. Intracellular uptake properties of GdSL were evaluated according to the intensity of ultrasound. Intracellular uptake of DOX for ultrasound-triggered GdSL was higher than that for non-ultrasound-triggered GdSL. The results of our study suggest that the paramagnetic and sonosensitive liposomes, GdSL, may provide a versatile platform for molecular imaging and targeted drug delivery.

Objectives

Childhood allergic diseases are a major concern because they lead to a heavy economic burden and poor quality of life. The purpose of this study was to investigate the prevalence of childhood atopic dermatitis, asthma, allergic rhinitis, and the comorbidity of allergic diseases in Seoul, Korea.

Methods

We conducted a cross-sectional survey between May and October 2010 to evaluate the prevalence of childhood allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis, using a questionnaire from the International Study of Asthma and Allergies in Childhood group. Each questionnaire was completed by the parent or guardian of a child.

Results

In the 31,201 children studied, the prevalence of atopic dermatitis symptoms in the past 12 months was 19.3% in children 0 to 3 years of age, 19.7% in children 4 to 6 years of age, 16.7% in children 7 to 9 years of age, and 14.5% in children 10 to 13 years of age (p for trend < 0.001). The prevalence of asthma in these age groups was 16.5%, 9.8%, 6.5%, and 5.4%, respectively (p for trend < 0.001). The prevalence of allergic rhinitis in these age groups was 28.5%, 38.0%, 38.5%, and 35.9%, respectively (p for trend = 0.043). The percentage of subjects with both atopic dermatitis and asthma, both asthma and allergic rhinitis, or both atopic dermatitis and allergic rhinitis was 2.5%, 4.7%, and 8.7%, respectively. The prevalence of comorbid allergic diseases decreased with age (p for trend < 0.001).

Conclusions

Our study revealed that the prevalence of some allergic diseases, such as atopic dermatitis and asthma, was relatively high in very young children and that all of the principal allergic diseases in children often co-exist.

Background

The Ampelopsis clade (Ampelopsis and its close allies) of the grape family Vitaceae contains ca. 43 species disjunctly distributed in Asia, Europe, North America, South America, Africa, and Australia, and is a rare example to study both the Northern and the Southern Hemisphere intercontinental disjunctions. We reconstruct the temporal and spatial diversification of the Ampelopsis clade to explore the evolutionary processes that have resulted in their intercontinental disjunctions in six continents.

Results

The Bayesian molecular clock dating and the likelihood ancestral area analyses suggest that the Ampelopsis clade most likely originated in North America with its crown group dated at 41.2 Ma (95% HPD 23.4 - 61.0 Ma) in the middle Eocene. Two independent Laurasian migrations into Eurasia are inferred to have occurred in the early Miocene via the North Atlantic land bridges. The ancestor of the Southern Hemisphere lineage migrated from North America to South America in the early Oligocene. The Gondwanan-like pattern of intercontinental disjunction is best explained by two long-distance dispersals: once from South America to Africa estimated at 30.5 Ma (95% HPD 16.9 - 45.9 Ma), and the other from South America to Australia dated to 19.2 Ma (95% HPD 6.7 - 22.3 Ma).

Conclusions

The global disjunctions in the Ampelopsis clade are best explained by a diversification model of North American origin, two Laurasian migrations, one migration into South America, and two post-Gondwanan long-distance dispersals. These findings highlight the importance of both vicariance and long distance dispersal in shaping intercontinental disjunctions of flowering plants.

Summary

Although Δ9-tetrahydrocannabinol (THC) and other mixed CB1/CB2 receptor agonists are well established to elicit antinociceptive effects, their psychomimetic actions and potential for abuse have dampened enthusiasm for their therapeutic development. Conversely, CB2 receptor-selective agonists have been shown to reduce pain and inflammation, without eliciting apparent cannabinoid behavioral effects. In the present study, we developed a novel ethyl sulfonamide THC analog, O-3223, and compared its pharmacological effects to those of the potent, mixed CB1/CB2 receptor agonist, CP55,940, in battery of preclinical pain models. Competitive cannabinoid receptor binding experiments revealed that O-3223 was approximately 80-fold more selective for CB2 than CB1 receptors. Additionally, O-3223 behaved as full CB2 receptor agonist in [35S]GTPγS binding. O-3223 reduced nociceptive behavior in both phases of the formalin test, reduced thermal hyperalgesia in the chronic constrictive injury of the sciatic nerve (CCI) model, and reduced edema and thermal hyperalgesia elicited by intraplantar injection of LPS. These effects were blocked by pretreatment with the CB2 receptor-selective antagonist SR144528, but not by the CB1 receptor antagonist, rimonabant. Unlike CP55,940, O-3223 did not elicit acute antinociceptive effects in the hot-plate test, hypothermia, or motor disturbances, as assessed in the rotarod test. These data indicate that the CB2 receptor-selective agonist, O-3223, reduces inflammatory and neuropathic nociception, without affecting basal nociception or eliciting overt behavioral effects. Moreover, this compound can serve as a template to develop new CB2 receptor agonists with increased receptor selectivity and increased potency in treating inflammatory and neuropathic pain.

Background

Natural killer (NK) cells activation has been reported to contribute to inflammation and liver injury during hepatitis B virus (HBV) infection both in transgenic mice and in patients. However, the role of NK cells in the process of HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating NK cell activation through recognition of specific human leukocyte antigen (HLA) class I allotypes.

Methodology/Principal Findings

To investigate whether KIR and HLA genes could influence the risk of HBV-associated HCC development, 144 HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The presence of 12 loci of KIR was detected individually. HLA-A, -B, -C loci were genotyped with high-resolution. HLA-C group 1 homozygote (OR = 2.02; p = 0.005), HLA-Bw4-80I (OR = 2.67; p = 2.0E-04) and combination of full-length form and 22 bp-deleted form of KIR2DS4 (KIR2DS4/1D) (OR = 1.89; p = 0.017) were found associated with HCC incidence. When the combined effects of these three genetic factors were evaluated, more risk factors were observed correlating with higher odds ratios for HCC incidence (P trend = 7.4E-05). Because all the risk factors we found have been reported to result in high NK cell functional potential by previous studies, our observations suggest that NK cell activation may contribute to HBV-associated HCC development.

Conclusions/Significance

In conclusion, this study has identified significant associations that suggest an important role for NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC surveillance and has implications for novel personalized therapy strategy development aiming at HCC prevention in HBV-infected patients.

The purpose of this study was to synthesize biocompatible polyvinylpyrrolidone (PVP)-coated iron oxide (PVP-IO) nanoparticles and to evaluate their efficacy as a magnetic resonance imaging (MRI) contrast agent. The PVP-IO nanoparticles were synthesized by a thermal decomposition method and characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and a superconducting quantum interface device (SQUID). The core size of the particles is about 8–10 nm and the overall size is around 20–30 nm. The measured r2 (reciprocal of T2 relaxation time) and r2∗ (reciprocal of T2∗ relaxation time) are 141.2 and 338.1 (s mM)−1, respectively. The particles are highly soluble and stable in various buffers and in serum. The macrophage uptake of PVP-IO is comparable to that of Feridex as measured by a Prussian blue iron stain and phantom study. The signal intensity of a rabbit liver was effectively reduced after intravenous administration of PVP-IO. Therefore PVP-IO nanoparticles are potentially useful for T2-weighted MR imaging.

Background and Aims

Rhododendron (Ericaceae) is a large woody genus in which hybridization is thought to play an important role in evolution and speciation, particularly in the Sino-Himalaya region where many interfertile species often occur sympatrically. Rhododendron agastum, a putative hybrid species, occurs in China, western Yunnan Province, in mixed populations with R. irroratum and R. delavayi.

Methods

Material of these taxa from two sites 400 km apart (ZhuJianYuan, ZJY and HuaDianBa, HDB) was examined using cpDNA and internal transcribed spacer (ITS) sequences, and amplified fragment length polymorphism (AFLP) loci, to test the possibility that R. agastum was in fact a hybrid between two of the other species. Chloroplast trnL-F and trnS-trnG sequences together distinguished R. irroratum, R. delavayi and some material of R. decorum, which is also considered a putative parent of R. agastum.

Key Results

All 14 R. agastum plants from the HDB site had the delavayi cpDNA haplotype, whereas at the ZJY site 17 R. agastum plants had this haplotype and four had the R. irroratum haplotype. R. irroratum and R. delavayi are distinguished by five unequivocal point mutations in their ITS sequences; every R. agastum accession had an additive pattern (double peaks) at each of these sites. Data from AFLP loci were acquired for between ten and 21 plants of each taxon from each site, and were analysed using a Bayesian approach implemented by the program NewHybrids. The program confirmed the identity of all accessions of R. delavayi, and all R. irroratum except one, which was probably a backcross. All R. agastum from HDB and 19 of 21 from ZJY were classified as F1 hybrids; the other two could not be assigned a class.

Conclusions

Rhododendron agastum represents populations of hybrids between R. irroratum and R. delavayi, which comprise mostly or only F1s, at the two sites examined. The sites differ in that at HDB there was no detected variation in cpDNA type or hybrid class, whereas at ZJY there was variation in both.

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

Objective

The aim of this study was to explore the role of farnesoid X receptor (FXR) in liver lipid metabolism of non-alcoholic fatty liver disease (NAFLD) patients.

Methods

In this study, pathology and clinical criteria confirmed NAFLD in patients. Fatty acid synthetase (FAS)-positive liver cells were visualized by laser scanning confocal microscopy. Levels of FXR, liver X receptor (LXR), sterol regulatory element binding protein 1C (SREBP-1C), and small heterodimer partner (SHP) proteins were detected by Western blot. FXR, LXR, and SHP mRNA levels were measured by real-time PCR.

Results

In patients with NAFLD, a significant positive relationship between the degree of hepatic steatosis and serum triglycerides and cholesterol (correlation coefficient > 0.5, P < 0.05) was seen. The NAFLD patients had more FAS protein in liver, which suggests that there could have been more of fatty acid synthesis in hepatic cells (P < 0.05). The levels of FXR protein and mRNA were decreased in patients with NAFLD (P < 0.05), while those of LXR and SREBP-1C were increased (P < 0.05). The levels of SREBP-1C positively correlated with the degree of hepatic steatosis. There were no differences between the levels of SHP protein and mRNA both in NAFLD patients and normal controls (P > 0.05).

Conclusion

Our data showed that the decreased expression of hepatic FXR is associated with an increased expression of LXR, SREBP-1C, and hepatic triglyceride synthesis; furthermore, increased SREBP-1C is associated with the degree of hepatic steatosis in the NAFLD patients.

The agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) induces nephrotoxicity characterized as polyuric renal failure and mediated via metabolites arising from oxidation of the succinimide ring. Recent findings have suggested that the stereochemical nature of NDPS metabolites may be an important factor in NDPS metabolite-induced nephrotoxicity. The purpose of the present study was to determine the role of stereochemistry in the in vivo nephrotoxicity induced by R-(+)- and S-(-)-N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (R- and S-NDHS) and the in vitro nephrotoxicity induced by their enantiomeric sulfate conjugates, R-(-)- and S-(+)-N-(3,5-dichlorophenyl)-2-hydroxysuccinimide-O-sulfate (R- and S-NSC). Male Fischer 344 rats (4 rats/group) were administered intraperitoneally (ip) an enantiomer of NDHS (0.05, 0.1 or 0.2 mmol/kg) or vehicle, and renal function monitored for 48 h. R-NDHS (0.1 or 0.2 mmol/kg) had little effect on renal function. In contrast, S-NDHS (0.1 mmol/kg) induced marked nephrotoxicity. The nephrotoxic potential of R- and S-NSC (0.5, 0.75 or 1.0 mM) was determined using freshly isolated rat renal cortical cells (IRCC, 3-4 × 106 cells/ml). Cytotoxicity was determined by measuring the release of lactate dehydrogenase (LDH) at the end of a 1 h incubation period. The LDH release observed in these studies was similar between R- and S-NSC. These results indicate that stereochemistry is an important factor for NDPS metabolite nephrotoxicity and that the role of stereochemistry, at least for NSC, occurs at extra-renal sites.

In complex multicellular eukaryotes such as animals and plants, horizontal gene transfer is commonly considered rare with very limited evolutionary significance. Here we show that horizontal gene transfer is a dynamic process occurring frequently in the early evolution of land plants. Our genome analyses of the moss Physcomitrella patens identified 57 families of nuclear genes that were acquired from prokaryotes, fungi or viruses. Many of these gene families were transferred to the ancestors of green or land plants. Available experimental evidence shows that these anciently acquired genes are involved in some essential or plant-specific activities such as xylem formation, plant defence, nitrogen recycling as well as the biosynthesis of starch, polyamines, hormones and glutathione. These findings suggest that horizontal gene transfer had a critical role in the transition of plants from aquatic to terrestrial environments. On the basis of these findings, we propose a model of horizontal gene transfer mechanism in nonvascular and seedless vascular plants.

Although horizontal gene transfer is prevalent in microorganisms, such sharing of genetic information is thought to be rare in land plants. Focusing on the sequenced moss species, Physcomitrella patens, these authors report genes acquired from microorganisms, which might have facilitated early evolution of land plants.