Age dependence of serum beta-N-acetylhexosaminidase (NAG) activity

Serum Nacetyl-beta-Dglucosaminidase (NAG; EC 3.2.1.30) is a hexosaminidase and may be a predictor of vascular injury, e.g., in infant respiratory distress syndrome, pneumonia, bronchopulmonary dysplasia and necrotizing enterocolitis. To estimate the new diagnostic prospects we have modified our urinary NAG assay. In this sensitive colorimetric microassay, VRAGlcNAc was used as a substrate. In the present study the age dependence of serum NAG activity was investigated in newborn babies, infants (124 months), children (218 years) and adults (1980 years). Serum NAG activity was found to be agedependent; it is higher in early childhood (1159 U/l) but decreases to a constant value at the age of 12 years. After the age of 2 years it is similar to adults NAG (1030 U/l). In pediatrics agematched reference ranges must be taken into consideration

Multiple QTL-effects of wheat Gpc-B1 locus on grain protein and micronutrient concentrations

Micronutrient malnutrition afflicts over three billion peopleworldwide and the numbers are continuously increasing. Developing genetically micronutrientenriched cereals, which are the predominant source of human dietary, is essential to alleviate malnutrition worldwide. Wheat chromosome 6B derived from wild emmerwheat [Triticum turgidum ssp. dicoccoides (Körn.) Thell] was previously reported to be a source for high Zn concentration in the grain. In the present study, recombinant chromosome substitution lines (RSLs), previously constructed for genetic and physical maps of Gpc-B1 (a 250-kb locus affecting grain protein concentration), were used to identify the effects of the Gpc-B1 locus on grain micronutrient concentrations. RSLs carrying the Gpc-B1 allele of T. dicoccoides accumulated on average 12% higher concentration of Zn, 18% higher concentration of Fe, 29% higher concentration of Mn and 38% higher concentration of protein in the grain as compared with RSLs carrying the allele from cultivated wheat (Triticum durum). Furthermore, the high grain Zn, Fe and Mn concentrations were consistently expressed in five different environments with an absence of genotype by environment interaction. The results obtained in the present study also confirmed the previously reported effect of the wild-type allele of Gpc-B1 on earlier senescence of flag leaves. We suggest that the Gpc-B1 locus is involved in more efficient remobilization of protein, zinc, iron and manganese from leaves to the grains, in addition to its effect on earlier senescence of the green tissues

Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease The PRESERVE Randomized Clinical Trial

Importance: Blood pressure lowering is considered neuroprotective in patients with cerebral small vessel disease, however more “intensive” regimens may increase cerebral hypoperfusion. We examined the effect of intensive vs. standard blood pressure treatment on cerebral perfusion in severe small vessel disease patients. Objective: To determine whether intensive vs. standard blood pressure lowering over 3 months causes decreased cerebral perfusion. Design, Setting and Participants: This randomised, parallel, controlled, blinded-outcomes clinical trial took place in 2 English university medical centres. A central, online randomisation system (1:1 ratio) allocated grouping. 70 hypertensive patients with MRI confirmed symptomatic lacunar infarct and confluent white matter hyperintensities were recruited between 2012 and 2015, and randomised (36/34 in standard/intensive arms). Analysable data were available in 62 patients, 33/29 in the standard/intensive groups respectively, for intention to treat analysis. This experiment examines the 3 month follow-up period. Intervention: Patients were randomised to “standard” (systolic=130-140mmHg) or “intensive” (systolic=<125mmHg) blood pressure targets, to be achieved through medication regimen changes. Main Outcome and Measure: Cerebral perfusion was determined using arterial spin labelling; the primary end point was change in global perfusion between baseline and 3 months, compared between treatment groups by ANOVA. Linear regression compared change in perfusion against change in blood pressure. MR scan analysis was blinded to treatment arm. Results: Patients were 69.3 years old (mean) and 59.7% male. Mean(SD) systolic blood pressure reduced by 8(12) and 27(17)mmHg in the standard/intensive groups, respectively (p<0.001), with achieved pressures of 141(13) and 126(10) mmHg respectively. Change in global perfusion did not differ between treatment arms: standard, mean(SD) (ml/min/100g)= -0.5(9.4); intensive, 0.7(8.6), partial ETA2= 0.004, 95% CI= -3.6–5.8, p= 0.63. No differences were observed when analysis examined grey/white matter only, or was confined to those achieving target blood pressure. The number of adverse events did not differ between treatment groups (standard/intensive mean(SD)= .21(.65)/.32(.75), p=.44). Conclusions and Relevance: Intensive blood pressure lowering did not reduce cerebral perfusion in severe small vessel disease.This study was funded by a joint Stroke Association/British Heart Foundation program grant (TSA BHF 2010/01). The study received additional support from the Newcastle Biomedical Research Centre, which is funded by the National Institute for Health Research (NIHR). Drs O’Brien, Ford, and Markus are supported by NIHR Senior Investigator awards. Drs O’Brien and Markus are also supported by the Cambridge University Hospitals NIHR Comprehensive Biomedical Research Centre

Deuteron and antideuteron production in Au+Au collisions at sqrt(s_NN)=200 GeV

The production of deuterons and antideuterons in the transverse momentum range 1.1 < p_T < 4.3 GeV/c at mid-rapidity in Au + Au collisions at sqrt(s_NN)=200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis comparing the deuteron and antideuteron spectra with those of protons and antiprotons, has been performed. The coalescence probability is equal for both deuterons and antideuterons and increases as a function of p_T, which is consistent with an expanding collision zone. Comparing (anti)proton yields p_bar/p = 0.73 +/- 0.01, with (anti)deuteron yields: d_bar/d = 0.47 +/- 0.03, we estimate that n_bar/n = 0.64 +/- 0.04.Comment: 326 authors, 6 pages text, 5 figures, 1 Table. Submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV

The invariant differential cross section for inclusive electron production in p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4 <= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo

In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study

Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions.

Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD)=0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD=0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight non-randomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD=0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P=0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses.GMK is supported by a Clinical Lecturer Starter Grant from the Academy of Medical Sciences, UK (grant no. 80354) and a Gosling Fellowship from the Royal College of Psychiatrists, UK (2015). GMK also received funding support from the Wellcome Trust 094790/Z/10/Z). PBJ acknowledges grant sup port from the Wellcome Trust (095844/Z/11/Z & 088869/Z/09/Z) and NIHR (RP-PG-0606-1335, Cambridge Biomedical Research Centre and CLAHRC East of England). RD has received grants from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health (grants R01 NS073939; R01 NS074999).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/mp.2016.16

The Emergence of a Lanthanide-rich Kilonova Following the Merger of Two Neutron Stars

We report the discovery and monitoring of the near-infrared counterpart (AT2017gfo) of a binary neutron-star merger event detected as a gravitational wave source by Advanced LIGO/Virgo (GW170817) and as a short gamma-ray burst by Fermi/GBM and Integral/SPI-ACS (GRB170817A). The evolution of the transient light is consistent with predictions for the behaviour of a "kilonova/macronova", powered by the radioactive decay of massive neutron-rich nuclides created via r-process nucleosynthesis in the neutron-star ejecta. In particular, evidence for this scenario is found from broad features seen in Hubble Space Telescope infrared spectroscopy, similar to those predicted for lanthanide dominated ejecta, and the much slower evolution in the near-infrared Ks-band compared to the optical. This indicates that the late-time light is dominated by high-opacity lanthanide-rich ejecta, suggesting nucleosynthesis to the 3rd r-process peak (atomic masses A~195). This discovery confirms that neutron-star mergers produce kilo-/macronovae and that they are at least a major - if not the dominant - site of rapid neutron capture nucleosynthesis in the universe

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm