Growth regulation of simian and human AIDS-related non-Hodgkin's lymphoma cell lines by TGF-β1 and IL-6

BACKGROUND: AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) is the second most frequent cancer associated with AIDS, and is a frequent cause of death in HIV-infected individuals. Experimental analysis of AIDS-NHL has been facilitated by the availability of an excellent animal model, i.e., simian Acquired Immunodeficiency Syndrome (SAIDS) in the rhesus macaque consequent to infection with simian immunodeficiency virus. A recent study of SAIDS-NHL demonstrated a lymphoma-derived cell line to be sensitive to the growth inhibitory effects of the ubiquitous cytokine, transforming growth factor-beta (TGF-beta). The authors concluded that TGF-beta acts as a negative growth regulator of the lymphoma-derived cell line and, potentially, as an inhibitory factor in the regulatory network of AIDS-related lymphomagenesis. The present study was conducted to assess whether other SAIDS-NHL and AIDS-NHL cell lines are similarly sensitive to the growth inhibitory effects of TGF-beta, and to test the hypothesis that interleukin-6 (IL-6) may represent a counteracting positive influence in their growth regulation. METHODS: Growth stimulation or inhibition in response to cytokine treatment was quantified using trypan blue exclusion or colorimetric MTT assay. Intracellular flow cytometry was used to analyze the activation of signaling pathways and to examine the expression of anti-apoptotic proteins and distinguishing hallmarks of AIDS-NHL subclass. Apoptosis was quantified by flow cytometric analysis of cell populations with sub-G1 DNA content and by measuring activated caspase-3. RESULTS: Results confirmed the sensitivity of LCL8664, an immunoblastic SAIDS-NHL cell line, to TGF-beta1-mediated growth inhibition, and further demonstrated the partial rescue by simultaneous treatment with IL-6. IL-6 was shown to activate STAT3, even in the presence of TGF-beta1, and thereby to activate proliferative and anti-apoptotic pathways. By comparison, human AIDS-NHL cell lines differed in their responsiveness to TGF-beta1 and IL-6. Analysis of a recently derived AIDS-NHL cell line, UMCL01-101, indicated that it represents immunoblastic AIDS-DLCBL. Like LCL-8664, UMCL01-101 was sensitive to TGF-beta1-mediated inhibition, rescued partially by IL-6, and demonstrated rapid STAT3 activation following IL-6 treatment even in the presence of TGF-beta1. CONCLUSION: These studies indicate that the sensitivity of immunoblastic AIDS- or SAIDS-DLBCL to TGF-beta1-mediated growth inhibition may be overcome through the stimulation of proliferative and anti-apoptotic signals by IL-6, particularly through the rapid activation of STAT3

The effect of Fucus vesiculosus, an edible brown seaweed, upon menstrual cycle length and hormonal status in three pre-menopausal women: a case report

BACKGROUND: Rates of estrogen-dependent cancers are among the highest in Western countries and lower in the East. These variations may be attributable to differences in dietary exposures such as higher seaweed consumption among Asian populations. The edible brown kelp, Fucus vesiculosus (bladderwrack), as well as other brown kelp species, lower plasma cholesterol levels. Since cholesterol is a precursor to sex hormone biosynthesis, kelp consumption may alter circulating sex hormone levels and menstrual cycling patterns. In particular, dietary kelp may be beneficial to women with or at high risk for estrogen-dependent diseases. To test this, bladderwrack was administered to three pre-menopausal women with abnormal menstrual cycling patterns and/or menstrual-related disease histories. CASE PRESENTATION: Intake of bladderwrack was associated with significant increases in menstrual cycle lengths, ranging from an increase of 5.5 to 14 days. In addition, hormone measurements ascertained for one woman revealed significant anti-estrogenic and progestagenic effects following kelp administration. Mean baseline 17β-estradiol levels were reduced from 626 ± 91 to 164 ± 30 pg/ml (P = 0.04) following 700 mg/d, which decreased further to 92.5.0 ± 3.5pg/ml (P = 0.03) with the1.4 g/d dose. Mean baseline progesterone levels rose from 0.58 ± 0.14 to 8.4 ± 2.6 ng/ml with the 700 mg/d dose (P = 0.1), which increased further to 16.8 ± 0.7 ng/ml with the 1.4 g/d dose (P = 0.002). CONCLUSIONS: These pilot data suggest that dietary bladderwrack may prolong the length of the menstrual cycle and exert anti-estrogenic effects in pre-menopausal women. Further, these studies also suggest that seaweed may be another important dietary component apart from soy that is responsible for the reduced risk of estrogen-related cancers observed in Japanese populations. However, these studies will need to be performed in well-controlled clinical trials to confirm these preliminary findings

Registered Replication Report: Dijksterhuis and van Knippenberg (1998)

Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence ("professor") subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence ("soccer hooligans"). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the "professor" category and those primed with the "hooligan" category (0.14%) and no moderation by gender

Crowdsourcing hypothesis tests: Making transparent how design choices shape research results

To what extent are research results influenced by subjective decisions that scientists make as they design studies? Fifteen research teams independently designed studies to answer fiveoriginal research questions related to moral judgments, negotiations, and implicit cognition. Participants from two separate large samples (total N > 15,000) were then randomly assigned to complete one version of each study. Effect sizes varied dramatically across different sets of materials designed to test the same hypothesis: materials from different teams renderedstatistically significant effects in opposite directions for four out of five hypotheses, with the narrowest range in estimates being d = -0.37 to +0.26. Meta-analysis and a Bayesian perspective on the results revealed overall support for two hypotheses, and a lack of support for three hypotheses. Overall, practically none of the variability in effect sizes was attributable to the skill of the research team in designing materials, while considerable variability was attributable to the hypothesis being tested. In a forecasting survey, predictions of other scientists were significantly correlated with study results, both across and within hypotheses. Crowdsourced testing of research hypotheses helps reveal the true consistency of empirical support for a scientific claim.</div

The high energy Universe at ultra-high resolution: the power and promise of X-ray interferometry

We propose the development of X-ray interferometry (XRI), to reveal the Universe at high energies with ultra-high spatial resolution. With baselines which can be accommodated on a single spacecraft, XRI can reach 100 μ as resolution at 10 Å (1.2 keV) and 20 μ as at 2 Å (6 keV), enabling imaging and imaging-spectroscopy of (for example) X-ray coronae of nearby accreting supermassive black holes (SMBH) and the SMBH ‘shadow’; SMBH accretion flows and outflows; X-ray binary winds and orbits; stellar coronae within ∼ 100 pc and many exoplanets which transit across them. For sufficiently luminous sources XRI will resolve sub-pc scales across the entire observable Universe, revealing accreting binary SMBHs and enabling trigonometric measurements of the Hubble constant with X-ray light echoes from quasars or explosive transients. A multi-spacecraft ‘constellation’ interferometer would resolve well below 1 μ as, enabling SMBH event horizons to be resolved in many active galaxies and the detailed study of the effects of strong field gravity on the dynamics and emission from accreting gas close to the black hole