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101.
The important role of the cytoskeletal scaffold is increasingly recognized in host-pathogen interactions. The cytoskeleton potentially functions as a weapon for both the plants defending themselves against fungal or oomycete parasites, and for the pathogens trying to overcome the resisting barrier of the plants. This concept, however, had not been investigated in marine algae so far. We are opening this scientific chapter with our study on the functional implications of the cytoskeleton in 3 filamentous brown algal species infected by the marine oomycete Eurychasma dicksonii. Our observations suggest that the cytoskeleton is involved in host defense responses and in fundamental developmental stages of E. dicksonii in its algal host.Oomycetes are important plant and animal pathogens and are the cause of significant crop losses every year. Hence, a plethora of studies with different cultivated and model plant species investigate the diversity of parasite infection pathways and host defense responses.1 However, little information is available on the interactions between algae and marine oomycetes, despite the epidemic outbreaks reported2 and the huge impact on intensive algal aquaculture.3Eurychasma dicksonii is a biotrophic, intracellular marine oomycete, capable to infect at least 45 species of brown seaweeds in laboratory cultures.4 Molecular data reveal that E. dicksonii has a basal phylogenetic position in the oomycete lineage.5,6 The basic stages of the infection are known: the attachment of the parasite spore to the host cell wall, the penetration of its cytoplasm into the host cell, the formation of a multinucleated, unwalled thallus, and zoosporogenesis.6 Hitherto, though, there was no knowledge about the role of cytoskeleton in the context of infection, which stimulated our research.In land plants, reorganization of the cytoskeleton is part of the reaction to infection by fungal pathogens. The rearrangement of the cytoplasm and the relocation of the nuclei and other organelles are accompanied by rapid rearrangements of the cytoskeletal elements.7 The plant cytoskeleton shows an extreme plasticity in order to serve the intracellular realignment.At the same time, this indicates that the plant cytoskeleton could be the parasite’s target by producing anti-cytoskeletal compounds in an effort to overcome plant resistance, a mechanism known in several fungal and oomycete pathogens of higher plants.8,9Consequently, the changes in microtubule (MT) organization are associated with both the plant defense and/or susceptibility toward oomycetes, respectively.10 Therefore, our research on the organization and role of cytoskeleton in the host and the parasite sheds some light into the enormous variability in the specificity of the recognition, defense, and infection mechanisms.  相似文献   
102.
The aim of this study was to assess and characterize the stability of multilamellar liposomes as a delivery vehicle for triamcinolone acetonide. A standardized preparation method for a liposomal delivery vehicle was developed, after varying composition and storage conditions, and assessing encapsulation efficiency and loss of active principle. The assessment of temperature as a factor in formula stability during storage showed that stability improved under refrigeration (4–6°C) (less early diffusion of active principle through the liposomal wall), in comparison with samples stored at room temperature. To improve stability, cholesterol was added to some formulae, which although resulting in a decrease in average encapsulation efficiency, mitigated subsequent losses of retained active principle (formulae 4, 5, and 6), in comparison with those without cholesterol (formulae 1, 2, and 3). This was evident both under refrigerated and room-temperature conditions. Finally, after testing the effects of adding an antioxidant and/or preservative to the formulae, a liposomal design was achieved with acceptable stability, vesicle dimensions, and encapsulation efficiency.  相似文献   
103.
The basic relationship between alcohol and women's sexual arousal – especially genital arousal – received little research attention for nearly 30 years (e.g. Wilson and Lawson, 1978) until very recently (e.g. George et al., 2009). To investigate hypotheses based on earlier findings and Alcohol Myopia Theory (AMT), two experiments evaluated the effects of high blood alcohol concentrations (BACs) and arousal instructional demands on indices of vaginal responding and self-reported sexual arousal. In Experiment 1, self-control instructions to maximize (versus suppress) arousal increased peak and average Vaginal Pulse Amplitude (VPA) change. Self-control also interacted with a target BAC of .08% (versus .00%) to influence latency to peak arousal onset: Intoxicated women instructed to maximize showed a shorter latency to peak arousal than did intoxicated women instructed to suppress; however, sober women showed an undifferentiated pattern. Also, in Experiment 1, the target BAC of .08% had no effect on VPA or subjective arousal measures. In Experiment 2, a target BAC of .10% (versus .00%) attenuated peak change and average change in VPA, but this dosage had no effects on latency to peak achieved arousal, or on subjective arousal. Instructions to maximize arousal (versus no instruction) had no effect on any arousal measures. Overall, among young moderate drinking women, alcohol had attenuating effects but only at the higher dosage. Maximize versus suppress instructions about arousal had predicted effects on arousal and interactive effects on latency, but only at the lower dosage. The findings highlight the importance of dosage and contextual factors in alcohol's impact on the variability of women's sexual responding.  相似文献   
104.
The interaction between women's hormonal condition and subjective, physiological, and behavioral indices of desire or arousal remains only partially explored, in spite of frequent reports from women about problems with a lack of sexual desire. The present study recruited premenopausal women at two sites, one in the United States and the other in the Netherlands, and incorporated various measures of acute changes in sexual desire and arousal. A sample of 46 women who met criteria for Hypoactive Sexual Desire Disorder (HSDD) was compared to 47 women who experienced no sexual problems (SF). Half of each group used oral contraceptives (OCs). The specific goal was to investigate whether there is a relationship between women's hormone levels and their genital and subjective sexual responsiveness. Background demographics and health variables, including oral contraceptive (OC) use, were recorded and hormones (total testosterone (T), free testosterone (FT), SHBG, and estradiol) were analyzed along with vaginal pulse amplitude and self-report measures of desire and arousal in response to sexual fantasy, visual sexual stimuli, and photos of men's faces. Self-reported arousal and desire were lower in the HSDD than the SF group, but only for women who were not using oral contraceptives. Relationships between hormones and sexual function differed depending on whether a woman was HSDD or not. In line with prior literature, FT was positively associated with physiological and subjective sexual arousal in the SF group. The HSDD women demonstrated the opposite pattern, in that FT was negatively associated with subjective sexual responsiveness. The findings suggest a possible alternative relationship between hormones and sexual responsiveness in women with HSDD who have characteristics similar to those in the present study.  相似文献   
105.
Chromatin structure and function are for a large part determined by the six members of the structural maintenance of chromosomes (SMC) protein family, which form three heterodimeric complexes: Smc1/3 (cohesin), Smc2/4 (condensin) and Smc5/6. Each complex has distinct and important roles in chromatin dynamics, gene expression and differentiation. In yeast and Drosophila, Smc6 is involved in recombinational repair, restarting collapsed replication forks and prevention of recombination in repetitive sequences such as rDNA and pericentromeric heterochromatin. Although such DNA damage control mechanisms, as well as highly dynamic changes in chromatin composition and function, are essential for gametogenesis, knowledge on Smc6 function in mammalian systems is limited. We therefore have investigated the role of Smc6 during mammalian spermatogonial differentiation, meiosis and subsequent spermiogenesis. We found that, during mouse spermatogenesis, Smc6 functions as part of meiotic pericentromeric heterochromatin domains that are initiated when differentiating spermatogonia become irreversibly committed toward meiosis. To our knowledge, we are the first to provide insight into how commitment toward meiosis alters chromatin structure and dynamics, thereby setting apart differentiating spermatogonia from the undifferentiated spermatogonia, including the spermatogonial stem cells. Interestingly, Smc6 is not essential for spermatogonial mitosis, whereas Smc6-negative meiotic cells appear unable to finish their first meiotic division. Importantly, during meiosis, we find that DNA repair or recombination sites, marked by γH2AX or Rad51 respectively, do not co-localize with the pericentromeric heterochromatin domains where Smc6 is located. Considering the repetitive nature of these domains and that Smc6 has been previously shown to prevent recombination in repetitive sequences, we hypothesize that Smc6 has a role in the prevention of aberrant recombination events between pericentromeric regions during the first meiotic prophase that would otherwise cause chromosomal aberrations leading to apoptosis, meiotic arrest or aneuploidies.  相似文献   
106.
Cartilage calcification contributes to the development and progression of osteoarthritis (OA). It has been well-investigated adiponectin regulates vascular calcification. The purpose of this study is to investigate the therapeutic value and the molecular mechanism of AdipoRon, an adiponectin receptor agonist, on the chondrocytes calcification. Primary chondrocytes were isolated and cultured from normal cartilage and OA cartilage. The calcification in tissues was evaluated by inductively coupled plasma/atomic emission spectroscopy and alizarin red S staining. The calcification in chondrocytes was determined using the alkaline phosphatase (ALP) staining and an ALP assay kit. The cellular effects of AdipoRon were assessed by immunofluorescence staining and Western blot analysis. We found that calcification was significantly increased in OA cartilage tissues and cells. Importantly, the degree of calcification and ALP activity of the OA chondrocytes was decreased upon the treatment with AdipoRon. The AdipoRon-induced cellular effects, including the reduction of the calcification of chondrocytes and improvement of autophagy, were blocked by dorsomorphin, an 5′-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. Moreover, autophagy activation by AdipoRon was mediated by the AMPK-mammalian target of rapamycin (mTOR) signaling pathway. Our results suggest that AdipoRon significantly alleviates the calcification of OA chondrocytes via activating AMPK-mTOR signaling to promote autophagy. Therefore, AdipoRon could be a potential therapeutic agent for the prevention and treatment of OA.  相似文献   
107.
The gastrointestinal peptide hormone ghrelin stimulates appetite in rodents and humans via hypothalamic actions. We discovered expression of ghrelin in a previously uncharacterized group of neurons adjacent to the third ventricle between the dorsal, ventral, paraventricular, and arcuate hypothalamic nuclei. These neurons send efferents onto key hypothalamic circuits, including those producing neuropeptide Y (NPY), Agouti-related protein (AGRP), proopiomelanocortin (POMC) products, and corticotropin-releasing hormone (CRH). Within the hypothalamus, ghrelin bound mostly on presynaptic terminals of NPY neurons. Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH). We propose that at these sites, release of ghrelin may stimulate the release of orexigenic peptides and neurotransmitters, thus representing a novel regulatory circuit controlling energy homeostasis.  相似文献   
108.

Background  

Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis.  相似文献   
109.

Background

The relationships between the infecting dengue serotype, primary and secondary infection, viremia and dengue severity remain unclear. This cross-sectional study examined these interactions in adult patients hospitalized with dengue in Ha Noi.

Methods and Findings

158 patients were enrolled between September 16 and November 11, 2008. Quantitative RT-PCR, serology and NS1 detection were used to confirm dengue infection, determine the serotype and plasma viral RNA concentration, and categorize infections as primary or secondary. 130 (82%) were laboratory confirmed. Serology was consistent with primary and secondary infection in 34% and 61%, respectively. The infecting serotype was DENV-1 in 42 (32%), DENV-2 in 39 (30%) and unknown in 49 (38%). Secondary infection was more common in DENV-2 infections (79%) compared to DENV-1 (36%, p<0.001). The proportion that developed dengue haemorrhagic fever (DHF) was 32% for secondary infection compared to 18% for primary infection (p = 0.14), and 26% for DENV-1 compared to 28% for DENV-2. The time until NS1 and plasma viral RNA were undetectable was shorter for DENV-2 compared to DENV-1 (p≤0.001) and plasma viral RNA concentration on day 5 was higher for DENV-1 (p = 0.03). Plasma viral RNA concentration was higher in secondary infection on day 5 of illness (p = 0.046). We didn''t find an association between plasma viral RNA concentration and clinical severity.

Conclusion

Dengue is emerging as a major public health problem in Ha Noi. DENV-1 and DENV-2 were the prevalent serotypes with similar numbers and clinical presentation. Secondary infection may be more common amongst DENV-2 than DENV-1 infections because DENV-2 infections resulted in lower plasma viral RNA concentrations and viral RNA concentrations were higher in secondary infection. The drivers of dengue emergence in northern Viet Nam need to be elucidated and public health measures instituted.  相似文献   
110.

Background

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in a small percentage of infected individuals. ATL is often associated with general immune suppression and an impaired HTLV-1-specific T-cell response, an important host defense system. We previously found that a small fraction of asymptomatic HTLV-1-carriers (AC) already showed impaired T-cell responses against the major target antigen, Tax. However, it is unclear whether the impaired HTLV-1 Tax-specific T-cell response in these individuals is an HTLV-1-specific phenomenon, or merely reflects general immune suppression. In this study, in order to characterize the impaired HTLV-1-specific T-cell response, we investigated the function of Tax-specific CD8+ T-cells in various clinical status of HTLV-1 infection.

Results

By using tetramers consisting of HLA-A*0201, -A*2402, or -A*1101, and corresponding Tax epitope peptides, we detected Tax-specific CD8+ T-cells in the peripheral blood from 87.0% of ACs (n = 20/23) and 100% of HAM/TSP patients (n = 18/18) tested. We also detected Tax-specific CD8+ T-cells in 38.1% of chronic type ATL (cATL) patients (n = 8/21), although its frequencies in peripheral blood CD8+ T cells were significantly lower than those of ACs or HAM/TSP patients. Tax-specific CD8+ T-cells detected in HAM/TSP patients proliferated well in culture and produced IFN-γ when stimulated with Tax peptides. However, such functions were severely impaired in the Tax-specific CD8+ T-cells detected in cATL patients. In ACs, the responses of Tax-specific CD8+ T-cells were retained in most cases. However, we found one AC sample whose Tax-specific CD8+ T-cells hardly produced IFN-γ, and failed to proliferate and express activation (CD69) and degranulation (CD107a) markers in response to Tax peptide. Importantly, the same AC sample contained cytomegalovirus (CMV) pp65-specific CD8+ T-cells that possessed functions upon CMV pp65 peptide stimulation. We further examined additional samples of two smoldering type ATL patients and found that they also showed dysfunctions of Tax-specific but not CMV-specific CD8+ T-cells.

Conclusions

These findings indicated that Tax-specific CD8+ T-cells were scarce and dysfunctional not only in ATL patients but also in a limited AC population, and that the dysfunction was selective for HTLV-1-specifc CD8+ T-cells in early stages.  相似文献   
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