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The development of progressively sophisticated tools complemented by the integration of live cell imaging enhances our understanding of the four-dimensional (4D) nucleome, revealing elaborate molecular interactions and chromatin states. Yet, the dynamics of chromosomes in relation to nuclear organelles or to each other across cell cycle in living cells are underexplored. We have developed photoconvertible GFP H3-Dendra2 stably expressing in PC3M cells. The nuclear lamina and perinucleolar associated heterochromatin or diffuse chromosome regions were photoconverted through a single-point activation using a confocal microscope. The results demonstrated a dynamic nature for both types of chromosomes in the same cell cycle and across mitosis. While some chromosome domains were heritably associated with either nuclear lamina or nucleoli, others changed alliance to different nuclear organelles postmitotically. In addition, co-photoconverted chromosome domains often do not stay together within the same cell cycle and across mitosis, suggesting a transient nature of chromosome neighborhoods. Long-range spreading and movement of chromosomes were also observed. Interestingly, when cells were treated with a low concentration of actinomycin D that inhibits Pol I transcription through intercalating GC-rich DNA, chromosome movement was significantly blocked. Treatment with another Pol I inhibitor, metarrestin, which does not impact DNA, had little effect on the movement, suggesting that the DNA structure itself plays a role in chromosome dynamics. Furthermore, inhibition of Pol II transcription with α-amanitin also reduced the chromosome movement, demonstrating that Pol II, but not Pol I transcription, is important for chromosome dynamics in the nucleus. [ABSTRACT FROM AUTHOR]

At present, tourism is counted among those industries which have gained global attention due to rapid growth. Hence, a constant diversification in terms of destination is needed in tourism development. The recent trends of industry highlight the demand of alternative tourism types, among which nature-related tourism appears to be an emerging concept. In this regard, the present article investigates the impact of economic conditions and sustainable rural development on the sustainability of tourism development in China. The current research has gathered secondary data from the World Bank from 1981 to 2020. The quartile autoregressive distributed lag model has been applied to test the association between the variables. The results revealed that GDP, inflation, FDI, exchange rate, energy use, gross savings, and sustainable rural development have a significant and positive association with the sustainability of tourism development in China. Findings offer managerial implications recommending the local government to focus on the sustainability of rural development and economic conditions that may lead to the implementation of tourism-related development projects. This study also guides the policymakers in establishing policies related to tourism development using different economic conditions and sustainable rural development. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3+ T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6–59.9%) at Pc 4 doses ranging from 0–300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6–81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300 nM, p ＜ 0.001 between 50 and 150 nM, n = 8). Treg uptake was diminished relative to other T cells. Cutaneous T cell lymphoma (CTCL) T cells appeared to take up somewhat more Pc 4 than normal resting T cells at 100 and 150 nm Pc 4. Confocal imaging revealed that Pc 4 localized in cytoplasmic organelles, with approximately half of the Pc 4 co-localized with mitochondria in T cells. Thus, Pc 4-PDT exerts an enhanced apoptotic effect on activated CD3+ T cells that may be exploited in targeting T cell-mediated skin diseases, such as cutaneous T cell lymphoma (CTCL) or psoriasis. [ABSTRACT FROM AUTHOR]

Rationale: The endogenous opioid and corticotropin-releasing hormone (CRH) systems, present in the central amygdala (CeA), are implicated in alcohol consumption. Objectives: The purpose of this study is to investigate the hypothesis that, in CeA, alcohol stimulates CRH release, which then stimulates β-endorphin release. Materials and methods: Rats were unilaterally implanted with a guide cannula to aim microdialysis probes in CeA. Experiment 1: rats received an intraperitoneal (IP) injection of various ethanol doses (0.0, 2.0, 2.4, or 2.8 g ethanol/kg body weight) and microdialysates were sampled at 30-min intervals to determine the effects over time of acute alcohol on the extracellular CRH concentrations in CeA. Experiment 2: phosphate-buffered saline, CRH, or CRH receptor (CRHR) antagonists (antalarmin or anti-sauvagine-30) was microinjected into CeA followed by a saline or 2.8 g/kg ethanol IP injection to determine the effects of CRHR activation or blockade in CeA on the basal and alcohol-stimulated release of β-endorphin. CRH and β-endorphin dialysate contents were determined using specific radioimmunoassays. Results: Acute alcohol induced a delayed increase in the extracellular CRH levels in CeA. Behavioural data showed no difference in locomotion between alcohol- and saline-treated rats. However, a transient increase in grooming was observed which did not correspond with alcohol-induced changes in CRH. Local CRH microinjections increased the extracellular β-endorphin concentrations in CeA. CRHR1 and CRHR2 blockade with microinjections of antalarmin and anti-sauvagine-30, respectively, attenuated the alcohol-induced increase of extracellular β-endorphin in CeA. Conclusions: Acute alcohol exerts indirect actions on CRH release and induced interactions of the CRH and β-endorphin systems in CeA. [ABSTRACT FROM AUTHOR]

The selectively bred lines of alcohol-preferring alko alcohol (AA) and alcohol-avoiding alko nonalcohol (ANA) rats have been used to demonstrate differences in relevant neurotransmitters which could account for their difference in alcohol consumption. Studies have demonstrated differences in distinct components of the endogenous opioid system in various brain regions associated with the process of reinforcement between the AA and ANA lines of rats. The goal of this current study was to investigate the hypotheses that the AA and ANA rats will show differences in the release of β-endorphin at the level of nucleus accumbens (NAC) and in locomotor activity in response to acute systemic administration of ethanol. AA and ANA rats were unilaterally implanted with a guide cannula to aim microdialysis probes at the level of NAC. Intraperitoneal injections of 0.0, 1.5, 2.0, and 2.5 g ethanol/kg body weight were administered. Dialysate samples were collected at 30-min intervals prior to and following the injection. Radioimmunoassay specific for β-endorphin was used to determine the dialysate β-endorphin content. The 2.5-g/kg ethanol dose induced a transient increase in extracellular β-endorphin at the level of NAC of AA but not of ANA rats. The 2.5-g/kg ethanol dose also attenuated locomotor activity in the AA but not in the ANA rats. The lack of an increase in the β-endorphin concentration in the NAC of ANA rats in response to ethanol may partially account for their lower alcohol consumption and lower alcohol-induced attenuation of locomotor activity compared to AA rats. [ABSTRACT FROM AUTHOR]

There is experimental evidence that indicates that the endogenous opioid system of the central nucleus of the amygdala (CeA) may mediate some of the reinforcing effects of ethanol. However, the precise interactions of ethanol with the endogenous opioid system at the level of the CeA have not been investigated. The aim of the current study was to investigate the hypothesis that acute systemic ethanol administration will increase the release of endogenous opioid peptides at the level of the CeA in a time- and dose-dependent manner. Rats were implanted with a unilateral guide cannula to aim microdialysis probes at the CeA. Intraperitoneal injections of saline and various doses of ethanol (0.8, 1.6, 2.0, 2.4, and 2.8 g ethanol/kg body weight) were administered to the rats. Dialysate samples were collected at 30-min intervals at distinct time points prior to and following treatment. Radioimmunoassays specific for β-endorphin, met-enkephalin, and dynorphin A1–8 were used to determine the effect of ethanol on the content of the opioid peptides in the dialysate. We report that the 2.8-g/kg dose of ethanol induced a long-lasting increase in β-endorphin release from 60 min onwards following administration and, later, an ongoing increase in dynorphin A1–8 release. None of the ethanol doses tested elicited significant changes in dialysate met-enkephalin content compared to the saline treatment. Acute systemic ethanol administration induced a dose- and time-dependent increase in β-endorphin and dynorphin A1–8 release at the level of the CeA, which may be involved in ethanol consumption. [ABSTRACT FROM AUTHOR]

Rationale: Guanfacine is an α2-adrenergic receptor agonist that has been shown to have beneficial effects on working memory and attentional functions in monkeys and in patients with attention deficit hyperactivity disorder. Objectives: The aim of this study was to further investigate the cognitive-enhancing properties of guanfacine using an established battery of tasks measuring executive and memory functions. Methods: Sixty healthy male volunteers were randomised into three groups. Cognitive testing was performed from +2 to +4 h after double-blind administration of a single oral dose of 1 or 2 mg of guanfacine or placebo. Results: Systolic blood pressure was significantly reduced by both doses of guanfacine at the end of the testing session. There were no statistically significant effects on any of the cognitive measures. Two trend effects were observed with poorer performance on digit span backward and slower 'Go' reaction times after guanfacine. Conclusion: This study found no improvement of prefrontal memory or executive functions after guanfacine. Negative effects on blood pressure and trend effects on digit span backward and go reaction time indicate a mild sedative effect of guanfacine at these doses, possibly via mechanisms of autoreceptor down-regulation. [ABSTRACT FROM AUTHOR]

Viral proteins inhibit apoptosis in host cells by a variety of mechanisms. This report proposes an additional mechanism, based on the interaction of a mutant mouse mammary tumor virus (MMTV) envelope glycoprotein precursor, Pr74, with the stress protein GRP78 (BiP) within the lumen of the endoplasmic reticulum (ER) (J. Biol. Chem. 268 7482-7488, 1993). We show that WEHI7.2 (W7.2) mouse lymphoma cells, which do not express Pr74, are more sensitive to cell death induction by the glucocorticoid hormone dexamethasone (dex), than W7MG1 cells, which were derived by infecting W7.2 cells with MMTV and therefore express Pr74 under control of the glucocorticoid-inducible MMTV promoter. Moreover, W7ENV/N cells, derived by stably transfecting W7.2 cells with a constitutively expressed cDNA encoding mutant Pr74, were less sensitive to dex-induced cell death than control transfectant W7-ENV/- cells. Among multiple W7-ENV/N subclones, susceptibility to dex-induced cell death was inversely related to the level of Pr74 synthesis. The interaction of Pr74 with GRP78 induces an increase in GRP78 synthesis. Thus, the repression of cell death associated with Pr74 expression may be secondary to elevated synthesis of GRP78, a stress protein previously implicated in protection against cell death. [ABSTRACT FROM AUTHOR]