Acute effects of nitrate-rich beetroot juice on blood pressure, hemostasis and vascular inflammation markers in healthy older adults: A randomized, placebo-controlled crossover study

Aging is associated with a vasoconstrictive, pro-coagulant, and pro-inflammatory profile of arteries and a decline in the bioavailability of the endothelium-derived molecule nitric oxide. Dietary nitrate elicits vasodilatory, anti-coagulant and anti-inflammatory effects in younger individuals, but little is known about whether these benefits are evident in older adults. We investigated the effects of 140 mL of nitrate-rich (HI-NI; containing 12.9 mmol nitrate) versus nitrate-depleted beetroot juice (LO-NI; containing ≤0.04 mmol nitrate) on blood pressure, blood coagulation, vascular inflammation markers, plasma nitrate and nitrite before, and 3 h and 6 h after ingestion in healthy older adults (five males, seven females, mean age: 64 years, age range: 57–71 years) in a randomized, placebo-controlled, crossover study. Plasma nitrate and nitrite increased 3 and 6 h after HI-NI ingestion (p < 0.05). Systolic, diastolic and mean arterial blood pressure decreased 3 h relative to baseline after HI-NI ingestion only (p < 0.05). The number of blood monocyte-platelet aggregates decreased 3 h after HI-NI intake (p < 0.05), indicating reduced platelet activation. The number of blood CD11b-expressing granulocytes decreased 3 h following HI-NI beetroot juice intake (p < 0.05), suggesting a shift toward an anti-adhesive granulocyte phenotype. Numbers of blood CD14++CD16+ intermediate monocyte subtypes slightly increased 6 h after HI-NI beetroot juice ingestion (p < 0.05), but the clinical implications of this response are currently unclear. These findings provide new evidence for the acute effects of nitrate-rich beetroot juice on circulating immune cells and platelets. Further long-term research is warranted to determine if these effects reduce the risk of developing hypertension and vascular inflammation with aging

Long-term effects of a protein-enriched diet on blood pressure in older women

Short-term randomised, controlled trials have found that dietary protein relative to carbohydrate can reduce blood pressure. Our objective was to investigate the effects on blood pressure of an increase in protein intake from whey over 2 years in women aged over 70 years. From the general population, 219 women aged between 70 and 80 years were recruited to a 2-year randomised, double-blind, placebo-controlled parallel-design trial: 181 women completed the trial to the end of year 2. Participants were randomly assigned to consume a daily whey protein-based beverage (protein) or an energy-matched low-protein high-carbohydrate beverage (control). Blood pressure measurements were performed at baseline, year 1 and year 2. For protein relative to control, the estimated mean net differences in protein and carbohydrate intakes were 18 (95 % CI 13, 23) and − 22 (95 % CI − 9, − 35) g/d at year 1, and 22 (95 % CI 17, 28) and − 18 (95 % CI − 6, − 31) g/d at year 2. Intention-to-treat analysis found no overall differences between groups in blood pressure (P>0.5). Net differences in systolic and diastolic blood pressure were – 2.3 (95 % CI – 5.3, 0.7) and – 1.5 (95 % CI – 3.6, 0.6) mmHg at year 1, and 1.6 (95 % CI – 1.5, 4.7) and 0.3 (95 % CI – 1.9, 2.4) mmHg at year 2. Similar differences in systolic and diastolic blood pressure at years 1 and 2 were observed with per-protocol analysis. Therefore, the present study did not provide evidence that a higher whey protein intake in older women can have prolonged effects on blood pressure

The physical constraints on a new LoBAL QSO at z=4.82

Very few low-ionization broad absorption line (LoBAL) QSOs have been found at high redshifts to date. One high-redshift LoBAL QSO, J0122+1216, was recently discovered at the Lijiang 2.4-m Telescope with an initial redshift determination of 4.76. Aiming to investigate its physical properties, we carried out follow-up observations in the optical and near-IR spectroscopy. Near-IR spectra from UKIRT and P200 confirms that it is a LoBAL, with a new redshift determination of $4.82\pm0.01$ based on the \mgii~ emission-line. The new \mgii~ redshift determination reveals strong blueshifts and asymmetry of the high-ionization emission lines. We estimated a black hole mass of $\sim 2.3\times 10^9 M_\odot$ and Eddington ratio of $\sim 1.0$ according to the empirical \mgii-based single-epoch relation and bolometric correction factor. It is possible that strong outflows are the result of an extreme quasar environment driven by the high Eddington ratio. A lower limit on the outflowing kinetic power ($>0.9\% L_{Edd}$) was derived from both emission and absorption lines, indicating these outflows play a significant role in the feedback process to regulate the growth of its black hole as well as host galaxy evolution.Comment: 12 pages, 10 figures. Accepted for publication in The Astrophysical Journa

Spontaneous DC Current Generation in a Resistively Shunted Semiconductor Superlattice Driven by a TeraHertz Field

We study a resistively shunted semiconductor superlattice subject to a high-frequency electric field. Using a balance equation approach that incorporates the influence of the electric circuit, we determine numerically a range of amplitude and frequency of the ac field for which a dc bias and current are generated spontaneously and show that this region is likely accessible to current experiments. Our simulations reveal that the Bloch frequency corresponding to the spontaneous dc bias is approximately an integer multiple of the ac field frequency.Comment: 8 pages, Revtex, 3 Postscript figure

ETV4 and ETV5 drive synovial sarcoma through cell cycle and DUX4 embryonic pathway control

Synovial sarcoma is an aggressive malignancy with no effective treatments for patients with metastasis. The synovial sarcoma fusion SS18-SSX, which recruits the SWI/SNF-BAF chromatin remodeling and polycomb repressive complexes, results in epigenetic activation of FGF receptor (FGFR) signaling. In genetic FGFR-knockout models, culture, and xenograft synovial sarcoma models treated with the FGFR inhibitor BGJ398, we show that FGFR1, FGFR2, and FGFR3 were crucial for tumor growth. Transcriptome analyses of BGJ398-treated cells and histological and expression analyses of mouse and human synovial sarcoma tumors revealed prevalent expression of two ETS factors and FGFR targets, ETV4 and ETV5. We further demonstrate that ETV4 and ETV5 acted as drivers of synovial sarcoma growth, most likely through control of the cell cycle. Upon ETV4 and ETV5 knockdown, we observed a striking upregulation of DUX4 and its transcriptional targets that activate the zygotic genome and drive the atrophy program in facioscapulohumeral dystrophy patients. In addition to demonstrating the importance of inhibiting all three FGFRs, the current findings reveal potential nodes of attack for the cancer with the discovery of ETV4 and ETV5 as appropriate biomarkers and molecular targets, and activation of the embryonic DUX4 pathway as a promising approach to block synovial sarcoma tumors

Exploring the Origin and Fate of the Magellanic Stream with Ultraviolet and Optical Absorption

(Abridged) We present an analysis of ionization and metal enrichment in the Magellanic Stream (MS), the nearest gaseous tidal stream, using HST/STIS and FUSE ultraviolet spectroscopy of two background AGN, NGC 7469 and Mrk 335. For NGC 7469, we include optical spectroscopy from VLT/UVES. In both sightlines the MS is detected in low-ion and high-ion absorption. Toward NGC 7469, we measure a MS oxygen abundance [O/H]_MS=[OI/HI]=-1.00+/-0.05(stat)+/-0.08(syst), supporting the view that the Stream originates in the SMC rather than the LMC. We use CLOUDY to model the low-ion phase of the Stream as a photoionized plasma using the observed Si III/Si II and C III/C II ratios. Toward Mrk 335 this yields an ionization parameter log U between -3.45 and -3.15 and a gas density log (n_H/cm^-3) between -2.51 and -2.21. Toward NGC 7469 we derive sub-solar abundance ratios for [Si/O], [Fe/O], and [Al/O], indicating the presence of dust in the MS. The high-ion column densities are too large to be explained by photoionization, but also cannot be explained by a single-temperature collisional-ionization model (equilibrium or non-equilibrium). This suggests the high-ion plasma is multi-phase. Summing over the low-ion and high-ion phases, we derive conservative lower limits on the ratio N(total H II)/N(H I) of >19 toward NGC 7469 and >330 toward Mrk 335, showing that along these two directions the vast majority of the Stream has been ionized. The presence of warm-hot plasma together with the small-scale structure observed at 21 cm provides evidence for an evaporative interaction with the hot Galactic corona. This scenario, predicted by hydrodynamical simulations, suggests that the fate of the MS will be to replenish the Galactic corona with new plasma, rather than to bring neutral fuel to the disk.Comment: Accepted for publication in ApJ. 18 pages, 7 figures, all in colo

Loss of Tet1 associated 5-hydroxymethylcytosine is concomitant with aberrant promoter hypermethylation in liver cancer

Aberrant hypermethylation of CpG islands (CGI) in human tumors occurs predominantly at repressed genes in the host tissue, but the preceding events driving this phenomenon are poorly understood. In this study, we temporally tracked epigenetic and transcriptomic perturbations which occur in a mouse model of liver carcinogenesis. Hypermethylated CGI events in the model were predicted by enrichment of the DNA modification 5-hydroxymethylcytosine (5hmC) and the histone H3 modification H3K27me3 at silenced promoters in the host tissue. During cancer progression, CGI underwent hypo-hydroxymethylation prior to hypermethylation, whilst retaining H3K27me3. In livers from mice deficient in Tet1, a tumor suppressor involved in cytosine demethylation, we observed a similar loss of promoter core 5hmC, suggesting that reduced Tet1 activity at CGI may contribute to epigenetic dysregulation observed during hepatocarcinogenesis. Consistent with this possibility, mouse liver tumors exhibited reduced Tet1 protein levels. Similar to humans, DNA methylation changes at CGI in mice did not appear to be direct drivers of hepatocellular carcinoma progression, rather, dynamic changes in H3K27me3 promoter deposition correlated strongly with tumor-specific activation and repression of transcription. Overall, our results suggest that loss of promoter-associated 5hmC in liver tumors licenses reprogramming of DNA methylation at silent CGI during progression

Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome.

BACKGROUND: Detection of a retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), has recently been reported in 67% of patients with chronic fatigue syndrome. We have studied a total of 170 samples from chronic fatigue syndrome patients from two UK cohorts and 395 controls for evidence of XMRV infection by looking either for the presence of viral nucleic acids using quantitative PCR (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation assay. RESULTS: We have not identified XMRV DNA in any samples by PCR (0/299). Some serum samples showed XMRV neutralising activity (26/565) but only one of these positive sera came from a CFS patient. Most of the positive sera were also able to neutralise MLV particles pseudotyped with envelope proteins from other viruses, including vesicular stomatitis virus, indicating significant cross-reactivity in serological responses. Four positive samples were specific for XMRV. CONCLUSIONS: No association between XMRV infection and CFS was observed in the samples tested, either by PCR or serological methodologies. The non-specific neutralisation observed in multiple serum samples suggests that it is unlikely that these responses were elicited by XMRV and highlights the danger of over-estimating XMRV frequency based on serological assays. In spite of this, we believe that the detection of neutralising activity that did not inhibit VSV-G pseudotyped MLV in at least four human serum samples indicates that XMRV infection may occur in the general population, although with currently uncertain outcomes