Work function of few layer graphene covered nickel thin films measured with Kelvin probe force microscopy

Few layer graphene and graphite are simultaneously grown on a similar to 100 nm thick polycrystalline nickel film. The work function of few layer graphene/Ni is found to be 4.15 eV with a variation of 50 meV by local measurements with Kelvin probe force microscopy. This value is lower than the work function of free standing graphene due to peculiar electronic structure resulting from metal 3d-carbon 2p(pi) hybridization. (C) 2016 AIP Publishing LLC

An updated analysis of NN elastic scattering data to 1.6 GeV

An energy-dependent and set of single-energy partial-wave analyses of $NN$ elastic scattering data have been completed. The fit to 1.6~GeV has been supplemented with a low-energy analysis to 400 MeV. Using the low-energy fit, we study the sensitivity of our analysis to the choice of $\pi NN$ coupling constant. We also comment on the possibility of fitting $np$ data alone. These results are compared with those found in the recent Nijmegen analyses. (Figures may be obtained from the authors upon request.)Comment: 17 pages of text, VPI-CAPS-7/

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

Impact of respirator versus surgical masks on SARS-CoV-2 acquisition in healthcare workers: a prospective multicentre cohort.

BACKGROUND There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) versus surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). METHODS Our prospective multicentre cohort enrolled HCW from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferentially worn mask type when caring for COVID-19 patients outside of aerosol-generating procedures. The impact of FFP2 on (1) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and (2) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. RESULTS We enrolled 3259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users; seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0.8, 95% CI 0.6-1.0) and seroconversion (adjusted odds ratio [aOR] 0.7, 95% CI 0.5-1.0); household exposure was the strongest risk factor (aHR 10.1, 95% CI 7.5-13.5; aOR 5.0, 95% CI 3.9-6.5). In subgroup analysis, FFP2 use was clearly protective among those with frequent (> 20 patients) COVID-19 exposure (aHR 0.7 for positive swab, 95% CI 0.5-0.8; aOR 0.6 for seroconversion, 95% CI 0.4-1.0). CONCLUSIONS Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients

Strain-Transcendent Immune Response to Recombinant Var2CSA DBL5-ε Domain Block P. falciparum Adhesion to Placenta-Derived BeWo Cells under Flow Conditions

BACKGROUND: Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi-domain protein var2CSA. Women become resistant to PAM, and develop strain-transcending immunity against CSA-binding parasites. The identification of var2CSA regions that could elicit broadly neutralizing and adhesion-blocking antibodies is a key step for the design of prophylactic vaccine strategies. METHODOLOGY: Escherichia coli expressed var2CSA DBL domains were refolded and purified prior to immunization of mice and a goat. Protein-G-purified antibodies were tested for their ability to block FCR3(CSA)-infected erythrocytes binding to placental (BeWo) and monkey brain endothelial (ScC2) cell lines using a flow cytoadhesion inhibition assay mimicking closely the physiological conditions present in the placenta at shear stress of 0.05 Pa. DBL5-ε, DBL6-ε and DBL5-6-ε induced cross-reactive antibodies using Alum and Freund as adjuvants, which blocked cytoadhesion at values ranging between 40 to 96% at 0.5 mg IgG per ml. Importantly, antibodies raised against recombinant DBL5-ε from 3 distinct parasites genotypes (HB3, Dd2 and 7G8) showed strain-transcending inhibition ranging from 38 to 64% for the heterologuous FCR3(CSA). CONCLUSIONS: Using single and double DBL domains from var2CSA and Alum as adjuvant, we identified recombinant subunits inducing an immune response in experimental animals which is able to block efficiently parasite adhesion in a flow cytoadhesion assay that mimics closely the erythrocyte flow in the placenta. These subunits show promising features for inclusion into a vaccine aiming to protect against PAM

Dissection of the Role of PfEMP1 and ICAM-1 in the Sensing of Plasmodium falciparum-Infected Erythrocytes by Natural Killer Cells

BACKGROUND: Host innate immunity contributes to malaria clinical outcome by providing protective inflammatory cytokines such as interferon-γ, and by shaping the adaptive immune response. Plasmodium falciparum (Pf) is the etiologic agent of the most severe forms of human malaria. Natural Killer (NK) cells are lymphocytes of the innate immune system that are the first effectors to produce interferon-γ in response to Pf. However, the molecular bases of Pf-NK cell recognition events are unknown. Our study focuses on the role of Pf erythrocyte membrane protein 1 (PfEMP1), a major Pf virulence factor. PfEMP1 is expressed on parasitized-erythrocytes and participates to vascular obstruction through the binding to several host receptors. PfEMP1 is also a pivotal target for host antibody response to Pf infection. METHODOLOGY/PRINCIPAL FINDINGS: Using genetically-engineered parasite mutant strains, a human genetic deficiency, and blocking antibodies, we identified two receptor-ligand pairs involved in two uncoupled events occurring during the sensing of Pf infection by NK cells. First, PfEMP1 interaction with one of its host receptor, chondroitin sulfate A, mediates the cytoadhesion of Pf-infected erythrocytes to human NK cell lines, but is not required for primary NK cell activation. Second, intercellular adhesion molecule-1 (ICAM-1), another host receptor for PfEMP1, is mandatory for NK cell interferon-γ response. In this case, ICAM-1 acts via its engagement with its host ligand, LFA-1, and not with PfEMP1, consistent with the obligatory cross-talk of NK cells with macrophages for their production of interferon-γ. CONCLUSION/SIGNIFICANCE: PfEMP1-independent but ICAM-1/LFA-1-dependent events occurring during NK cell activation by Pf highlight the fundamental role of cellular cooperation during innate immune response to malaria

Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects.</p> <p>Methods</p> <p>It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry.</p> <p>Results</p> <p>GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls.</p> <p>Conclusion</p> <p>This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages.</p

Identification of the Plasmodium berghei resistance locus 9 linked to survival on chromosome 9

Background: One of the main causes of mortality from severe malaria in Plasmodium falciparum infections is cerebral malaria (CM). An important host genetic component determines the susceptibility of an individual to develop CM or to clear the infection and become semi-immune. As such, the identification of genetic loci associated with susceptibility or resistance may serve to modulate disease severity. Methodology The Plasmodium berghei mouse model for experimental cerebral malaria (ECM) reproduces several disease symptoms seen in human CM, and two different phenotypes, a susceptible (FVB/NJ) and a resistant mouse strain (DBA/2J), were examined. Results: FVB/NJ mice died from infection within ten days, whereas DBA/2J mice showed a gender bias: males survived on average nineteen days and females either died early with signs of ECM or survived for up to three weeks. A comparison of brain pathology between FVB/NJ and DBA/2J showed no major differences with regard to brain haemorrhages or the number of parasites and CD3+ cells in the microvasculature. However, significant differences were found in the peripheral blood of infected mice: For example resistant DBA/2J mice had significantly higher numbers of circulating basophils than did FVB/NJ mice on day seven. Analysis of the F2 offspring from a cross of DBA/2J and FVB/NJ mice mapped the genetic locus of the underlying survival trait to chromosome 9 with a Lod score of 4.9. This locus overlaps with two previously identified resistance loci (char1 and pymr) from a blood stage malaria model. Conclusions: Survival best distinguishes malaria infections between FVB/NJ and DBA/2J mice. The importance of char1 and pymr on chromosome 9 in malaria resistance to P. berghei was confirmed. In addition there was an association of basophil numbers with survival

Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines

BACKGROUND: Mediterranean societies, with diets rich in vitamin E isoforms, have a lower risk for colon cancer than those of northern Europe and the Americas. Vitamin E rich diets may neutralize free radicals generated by fecal bacteria in the gut and prevent DNA damage, but signal transduction activities can occur independent of the antioxidant function. The term vitamin E represents eight structurally related compounds, each differing in their potency and mechanisms of chemoprevention. The RRR-γ-tocopherol isoform is found primarily in the US diet, while RRR-α-tocopherol is highest in the plasma. METHODS: The effectiveness of RRR-α- and RRR-γ-tocopherol at inhibiting cell growth and inducing apoptosis in colon cancer cell lines with varying molecular characteristics (SW480, HCT-15, HCT-116 and HT-29) and primary colon cells (CCD-112CoN, nontransformed normal phenotype) was studied. Colon cells were treated with and without RRR-α- or RRR-γ-tocopherol using varying tocopherol concentrations and time intervals. Cell proliferation and apoptosis were measured using the trypan blue assay, annexin V staining, DNA laddering and caspase activation. RESULTS: Treatment with RRR-γ-tocopherol resulted in significant cell death for all cancer cell lines tested, while RRR-α-tocopherol did not. Further, RRR-γ-tocopherol treatment showed no cytotoxicity to normal colon cells CCD-112CoN at the highest concentration and time point tested. RRR-γ-tocopherol treatment resulted in cleavage of PARP, caspase 3, 7, and 8, but not caspase 9. Differences in the percentage cell death and apoptosis were observed in different cell lines suggesting that molecular differences in these cell lines may influence the ability of RRR-γ-tocopherol to induce cell death. CONCLUSION: This is the first study to demonstrate that multiple colon cancer cell lines containing varying genetic alterations will under go growth reduction and apoptosis in the presence of RRR-γ-tocopherol without damage to normal colon cells. The amount growth reduction was dependent upon the molecular signatures of the cell lines. Since RRR-γ-tocopherol is effective at inhibition of cell proliferation at both physiological and pharmacological concentrations dietary RRR-γ-tocopherol may be chemopreventive, while pharmacological concentrations of RRR-γ-tocopherol may aid chemotherapy without toxic effects to normal cells demonstrated by most chemotherapeutic agents