Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD

Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice. Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation. We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis. Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD), cigarette-smoking and other lung inflammatory diseases. We now show that zinc is a factor in impaired macrophage efferocytosis in COPD. Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking. Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN. Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins. Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role. We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency. There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels. Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages. We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2 transporters responding differently to zinc deficiency signals and that these play important roles in macrophage efferocytosis

Belowground DNA-based techniques: untangling the network of plant root interactions

Contains fulltext : 91591.pdf (publisher's version ) (Closed access)7 p

Quasi-particle interference and superconducting gap in a high-temperature superconductor Ca2-xNaxCuO2Cl2

High-transition-temperature (high-Tc) superconductivity is ubiquitous in the cuprates containing CuO2 planes but each cuprate has its own character. The study of the material dependence of the d-wave superconducting gap (SG) should provide important insights into the mechanism of high-Tc. However, because of the 'pseudogap' phenomenon, it is often unclear whether the energy gaps observed by spectroscopic techniques really represent the SG. Here, we report spectroscopic imaging scanning tunneling microscopy (SI-STM) studies of nearly-optimally-doped Ca2-xNaxCuO2Cl2 (Na-CCOC) with Tc = 25 ~ 28 K. They enable us to observe the quasi-particle interference (QPI) effect in this material, through which unambiguous new information on the SG is obtained. The analysis of QPI in Na-CCOC reveals that the SG dispersion near the gap node is almost identical to that of Bi2Sr2CaCu2Oy (Bi2212) at the same doping level, while Tc of Bi2212 is 3 times higher than that of Na-CCOC. We also find that SG in Na-CCOC is confined in narrower energy and momentum ranges than Bi2212. This explains at least in part the remarkable material dependence of TcComment: 13pages, 4fig

Rehabilitation Enablement in Chronic Heart Failure—a facilitated self-care rehabilitation intervention in patients with heart failure with preserved ejection fraction (REACH-HFpEF) and their caregivers:rationale and protocol for a single-centre pilot randomised controlled trial

This is the final version of the article. Available from the publisher via the DOI in this record.INTRODUCTION: The Rehabilitation EnAblement in CHronic Heart Failure in patients with Heart Failure (HF) with preserved ejection fraction (REACH-HFpEF) pilot trial is part of a research programme designed to develop and evaluate a facilitated, home-based, self-help rehabilitation intervention to improve self-care and quality of life (QoL) in heart failure patients and their caregivers. We will assess the feasibility of a definitive trial of the REACH-HF intervention in patients with HFpEF and their caregivers. The impact of the REACH-HF intervention on echocardiographic outcomes and bloodborne biomarkers will also be assessed. METHODS AND ANALYSIS: A single-centre parallel two-group randomised controlled trial (RCT) with 1:1 individual allocation to the REACH-HF intervention plus usual care (intervention) or usual care alone (control) in 50 HFpEF patients and their caregivers. The REACH-HF intervention comprises a REACH-HF manual with supplementary tools, delivered by trained facilitators over 12 weeks. A mixed methods approach will be used to assess estimation of recruitment and retention rates; fidelity of REACH-HF manual delivery; identification of barriers to participation and adherence to the intervention and study protocol; feasibility of data collection and outcome burden. We will assess the variance in study outcomes to inform a definitive study sample size and assess methods for the collection of resource use and intervention delivery cost data to develop the cost-effectiveness analyses framework for any future trial. Patient outcomes collected at baseline, 4 and 6 months include QoL, psychological well-being, exercise capacity, physical activity and HF-related hospitalisation. Caregiver outcomes will also be assessed, and a substudy will evaluate impact of the REACH-HF manual on resting global cardiovascular function and bloodborne biomarkers in HFpEF patients. ETHICS AND DISSEMINATION: The study is approved by the East of Scotland Research Ethics Service (Ref: 15/ES/0036). Findings will be disseminated via journals and presentations to clinicians, commissioners and service users. TRIAL REGISTRATION NUMBER: ISRCTN78539530; Pre-results .This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-1210-12004). NB, CA, CJG and RST are also supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust; KJ by CLAHRC West Midlands and SS by CLAHRC East-Midlands. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Healt

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

VLASSICK: The VLA Sky Survey in the Central Kiloparsec

At a distance of 8 kpc, the center of our Galaxy is the nearest galactic nucleus, and has been the subject of numerous key projects undertaken by great observatories such as Chandra, Spitzer, and Herschel. However, there are still no surveys of molecular gas properties in the Galactic center with less than 30" (1 pc) resolution. There is also no sensitive polarization survey of this region, despite numerous nonthermal magnetic features apparently unique to the central 300 parsecs. In this paper, we outline the potential the VLASS has to fill this gap. We assess multiple considerations in observing the Galactic center, and recommend a C-band survey with 10 micro-Jy continuum RMS and sensitive to molecular gas with densities greater than 10^4 cm^{-3}, covering 17 square degrees in both DnC and CnB configurations ( resolution ~5"), totaling 750 hours of observing time. Ultimately, we wish to note that the upgraded VLA is not just optimized for fast continuum surveys, but has a powerful correlator capable of simultaneously observing continuum emission and dozens of molecular and recombination lines. This is an enormous strength that should be fully exploited and highlighted by the VLASS, and which is ideally suited for surveying the center of our Galaxy

Outcomes of synchronous and metachronous bilateral small renal masses (< 4 cm):a population‑based cohort study

Objectives: To report longitudinal outcomes of a population based cohort of patients diagnosed with bilateral small renal masses from a period of over 11 years.Patients and Methods: Consecutive patients diagnosed with bilateral small renal masses (synchronous or metachronous) of a defined geographical area were recorded in a large database (TUCAN database) between January 2005 and December 2016. Patients had a unique identifier number and followed during this period using an agreed upon protocol. Clinicopathological characteristics and outcomes of bilateral small renal masses on active surveillance were analysed and compared to propensity score matched sporadic unilateral small renal masses. Data were analysed for renal mass growth rate, rate of intervention and development of metastatic disease and patient survival.Results: A total of 1060 patients were diagnosed with renal cancer, of which bilateral small renal masses accounted for 70 (6.6%) cases. Synchronous SRMs were observed in 63 patients, whereas metachronous lesions were found in seven patients during the study period. Metachronous lesion mean time to appearance was 62 ± 41 months (range, 9 to 149 months). While most cases were sporadic, four were found to be hereditary. Growth rate of bilateral small renal masses did not differ from that of unilateral sporadic small renal masses. Similarly, there were no differences between the groups for rate of interventions and survival.Conclusion: Progression, rate of metastases and survival for patients diagnosed with bilateral small renal masses is similar to those diagnosed with unilateral disease

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV