Symmetric expression of ohnologs encoding conserved antiviral responses in tetraploid common carp suggest absence of subgenome dominance after whole genome duplication.

Allopolyploids often experience subgenome dominance, with one subgenome showing higher levels of gene expression and greater gene retention. Here, we address the functionality of both subgenomes of allotetraploid common carp (Cyprinus carpio) by analysing a functional network of interferon-stimulated genes (ISGs) crucial in anti-viral immune defence. As an indicator of subgenome dominance we investigated retainment of a core set of ohnologous ISGs. To facilitate our functional genomic analysis a high quality genome was assembled (WagV4.0). Transcriptome data from an in vitro experiment mimicking a viral infection was used to infer ISG expression. Transcriptome analysis confirmed induction of 88 ISG ohnologs on both subgenomes. In both control and infected states, average expression of ISG ohnologs was comparable between the two subgenomes. Also, the highest expressing and most inducible gene copies of an ohnolog pair could be derived from either subgenome. We found no strong evidence of subgenome dominance for common carp.

Optical Control of a Single Nuclear Spin in the Solid State.

We demonstrate a novel method for coherent optical manipulation of individual nuclear spins in the solid state, mediated by the electronic states of a proximal quantum emitter. Specifically, using the nitrogen-vacancy (NV) color center in diamond, we demonstrate control of a proximal ^{14}N nuclear spin via an all-optical Raman technique. We evaluate the extent to which the intrinsic physical properties of the NV center limit the performance of coherent control, and we find that it is ultimately constrained by the relative rates of transverse hyperfine coupling and radiative decay in the NV center's excited state. Possible extensions and applications to other color centers are discussed.

Energy Flux Densities near the Electron Dissipation Region in Asymmetric Magnetopause Reconnection.

Magnetic reconnection is of fundamental importance to plasmas because of its role in releasing and repartitioning stored magnetic energy. Previous results suggest that this energy is predominantly released as ion enthalpy flux along the reconnection outflow. Using Magnetospheric Multiscale data we find the existence of very significant electron energy flux densities in the vicinity of the magnetopause electron dissipation region, orthogonal to the ion energy outflow. These may significantly impact models of electron transport, wave generation, and particle acceleration.

Evolution of models to support community and policy action with science: Balancing pastoral livelihoods and wildlife conservation in savannas of East Africa.

We developed a "continual engagement" model to better integrate knowledge from policy makers, communities, and researchers with the goal of promoting more effective action to balance poverty alleviation and wildlife conservation in 4 pastoral ecosystems of East Africa. The model involved the creation of a core boundary-spanning team, including community facilitators, a policy facilitator, and transdisciplinary researchers, responsible for linking with a wide range of actors from local to global scales. Collaborative researcher-facilitator community teams integrated local and scientific knowledge to help communities and policy makers improve herd quality and health, expand biodiversity payment schemes, develop land-use plans, and fully engage together in pastoral and wildlife policy development. This model focused on the creation of hybrid scientific-local knowledge highly relevant to community and policy maker needs. The facilitation team learned to be more effective by focusing on noncontroversial livelihood issues before addressing more difficult wildlife issues, using strategic and periodic engagement with most partners instead of continual engagement, and reducing costs by providing new scientific information only when deemed essential. We conclude by examining the role of facilitation in redressing asymmetries in power in researcher-community-policy maker teams, the role of individual values and character in establishing trust, and how to sustain knowledge-action links when project funding ends.

Donor deferral policies for men who have sex with men: past, present and future.

We review the history and evolution of blood donor criteria for men who have sex with men (MSM). Deferral policies in many jurisdictions, including Australia, New Zealand, Canada, the United States, Brazil and many western European countries are based on a period of abstinence from MSM, often of 12 months duration. Several countries (Italy, Spain and Portugal) defer donors based on sexual behaviours considered to be at high risk, regardless of whether the partner is same sex or opposite sex. Compliance is a key determinant in the efficacy of any deferral policy. We summarize research themes and strategies discussed at a January 2017 meeting held in Toronto, Canada, to provide an evidence basis for future policy changes.

Guide Field Reconnection: Exhaust Structure and Heating.

Magnetospheric Multiscale observations are used to probe the structure and temperature profile of a guide field reconnection exhaust ~100 ion inertial lengths downstream from the X-line in the Earth's magnetosheath. Asymmetric Hall electric and magnetic field signatures were detected, together with a density cavity confined near 1 edge of the exhaust and containing electron flow toward the X-line. Electron holes were also detected both on the cavity edge and at the Hall magnetic field reversal. Predominantly parallel ion and electron heating was observed in the main exhaust, but within the cavity, electron cooling and enhanced parallel ion heating were found. This is explained in terms of the parallel electric field, which inhibits electron mixing within the cavity on newly reconnected field lines but accelerates ions. Consequently, guide field reconnection causes inhomogeneous changes in ion and electron temperature across the exhaust.

Magnetospheric Multiscale Satellites Observations of Parallel Electric Fields Associated with Magnetic Reconnection.

We report observations from the Magnetospheric Multiscale satellites of parallel electric fields (E_{∥}) associated with magnetic reconnection in the subsolar region of the Earth's magnetopause. E_{∥} events near the electron diffusion region have amplitudes on the order of 100 mV/m, which are significantly larger than those predicted for an antiparallel reconnection electric field. This Letter addresses specific types of E_{∥} events, which appear as large-amplitude, near unipolar spikes that are associated with tangled, reconnected magnetic fields. These E_{∥} events are primarily in or near a current layer near the separatrix and are interpreted to be double layers that may be responsible for secondary reconnection in tangled magnetic fields or flux ropes. These results are telling of the three-dimensional nature of magnetopause reconnection and indicate that magnetopause reconnection may be often patchy and/or drive turbulence along the separatrix that results in flux ropes and/or tangled magnetic fields.

Development of standard definitions for surveillance of complications related to blood donation.

Standard definitions of donor reactions allow each blood establishment to monitor donor adverse events and compare with other organizations to develop best practices. The ISBT Haemovigilance Working Party leads a multi-organizational effort to update the 2008 ISBT standard for surveillance of complications related to blood donation. Revised definitions have been developed and endorsed by the ISBT, AABB, International Haemovigilance Network (IHN) and other international organizations.

Phonon-induced population dynamics and intersystem crossing in nitrogen-vacancy centers.

We report direct measurement of population dynamics in the excited state manifold of a nitrogen-vacancy (NV) center in diamond. We quantify the phonon-induced mixing rate and demonstrate that it can be completely suppressed at low temperatures. Further, we measure the intersystem crossing (ISC) rate for different excited states and develop a theoretical model that unifies the phonon-induced mixing and ISC mechanisms. We find that our model is in excellent agreement with experiment and that it can be used to predict unknown elements of the NV center's electronic structure. We discuss the model's implications for enhancing the NV center's performance as a room-temperature sensor.

Donor attention to reading materials.

BACKGROUND AND OBJECTIVES: Mandatory predonation reading materials inform donors about risk factors for transmissible disease, possible complications of donation and changes to the donation process. We aimed to assess the attention to predonation reading materials and factors which may affect attention. MATERIALS AND METHODS: A national survey in 2008 of 18,108 blood donors asked about self-assessed attention to reading the materials. In face-to-face interviews, 441 donors completed additional questions about reading the materials and a literacy test. Qualitative interviews of 27 donors assessed their approach to reading. RESULTS: In the national survey, most of the first-time donors said they read all or most of the materials (90.9% first-time vs. 57.6% repeat donors, P < 0.001) and 66% vs. 23.1% reported reading them carefully (P < 0.001). In face-to-face interviews comparing those who read materials carefully, skimmed or did not read, most knew that donors are informed of positive transmissible disease test results (97.1%, 95.5, 98.0 P > 0.05), but fewer recalled seeing the definition of sex (77.2%, 56.9, 24.2 P < 0.001). Literacy was poor (30.5% frustration level, 60.3% instructional, 9.2% independent) but similar when those who read materials carefully, skimmed or did not read were compared (P > 0.05). Qualitative interviews showed that donors are reluctant to read any more than necessary and decide based on perceived importance or relevance. CONCLUSION: Attention to predonation reading materials tends to be better among first-time donors. The effectiveness is limited by low motivation to read, especially for repeat donors, as well as poor literacy.

Effect of hyperbaric oxygen therapy on amphotericin-B induced acute renal failure in rats.

AIM: Acute renal injury may occur after amphotericin B (AmB) administration. The hypothesized injury mechanism is renal vasoconstriction and direct toxic damage. Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischemic events but not for acute renal failure (ARF). The aim of this study was to investigate the role of HBO therapy in AmB induced ARF. METHODS: ARF was induced in 41 Sprague-Dawley rats by a single dose of 75 mg/kg AmB. The rats were randomly divided into two groups; one group was treated with daily HBO for 3 consecutive days. The control group received no HBO treatment. Parameters of renal function were taken on the 5th day after AmB administration. RESULTS: Forty-one rats were treated with AmB, 21 received HBO and 20 served as controls. Body weight loss following the administration of AmB was 13.5+14.7% in the HBO treated rats, as opposed to 24.6+5% in the control group (P=0.004). Serum creatinine and urea were 0.49+0.13 mg/dL and 200.63+87.82 mg/dL in the treatment group and 0.70+0.22 mg/dL and 368.01+169.35 mg/dL, respectively in the control (P=0.001). CONCLUSION: In this model of AmB-induced ARF, HBO treatment alleviated renal injury as reflected by changes in serum creatinine and urea levels.

Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary.

BACKGROUND: Although respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease. OBJECTIVE: To evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising 11 of the 14 items in the Exacerbations of Chronic Pulmonary Disease Tool (EXACT). METHODS: Qualitative: patient focus group and interviews to address content validity. Quantitative: secondary data analyses to test reliability and validity. RESULTS: Qualitative: n=84; mean (SD) age 65 (10) years, FEV1 1.2(0.4) L; 44% male. Subject descriptions of their respiratory symptoms were consistent with E-RS content and structure. Quantitative: n=188; mean (SD) age 66 (10) years, FEV1 1.2(0.5) L; 50% male. Factor analysis (FA) showed 3 subscales: RS-Breathlessness, RS-Cough & Sputum, and RS-Chest Symptoms; second-order FA supported a general factor and total score. Reliability (total and subscales): 0.88, 0.86, 0.73, 0.81; 2-day test-retest ICC: 0.90, 0.86, 0.87, 0.82, respectively. VALIDITY: Total scores correlated significantly (p < 0.0001) with SGRQ Total (r=0.75), Symptoms (r=0.66), Activity (r=0.57), Impact (r=0.70) scores; subscale correlations were also significant (r=0.26, p < 0.05 (RS-Chest Symptoms with Activity) to r=0.69, p < 0.0001 (RS-Cough & Sputum with Symptoms). RS-Breathlessness correlated with rescue medication use (r=0.32, p < 0.0001), clinician-reported mMRC (r=0.33, p < 0.0001), and FEV1% predicted (r=-0.17, p < 0.05). E-RS scores differentiated groups based on chronic bronchitis diagnosis (p < 0.01-0.001), smoking status (p < 0.05-0.001), and rescue medication use (p < 0.05-0.0001). CONCLUSIONS: Results suggest the RS-Total is a reliable and valid instrument for evaluating respiratory symptom severity in stable COPD. Further study of sensitivity to change is warranted.

Cerenkov emission of quasiparallel whistlers by fast electron phase-space holes during magnetic reconnection.

Kinetic simulations of magnetotail reconnection have revealed electromagnetic whistlers originating near the exhaust boundary and propagating into the inflow region. The whistler production mechanism is not a linear instability, but rather is Cerenkov emission of almost parallel whistlers from localized moving clumps of charge (finite-size quasiparticles) associated with nonlinear coherent electron phase space holes. Whistlers are strongly excited by holes without ever growing exponentially. In the simulation the whistlers are emitted in the source region from holes that accelerate down the magnetic separatrix towards the x line. The phase velocity of the whistlers vφ in the source region is everywhere well matched to the hole velocity vH as required by the Cerenkov condition. The simulation shows emission is most efficient near the theoretical maximum vφ=half the electron Alfven speed, consistent with the new theoretical prediction that faster holes radiate more efficiently. While transferring energy to whistlers the holes lose coherence and dissipate over a few local ion inertial lengths. The whistlers, however, propagate to the x line and out over many 10's of ion inertial lengths into the inflow region of reconnection. As the whistlers pass near the x line they modulate the rate at which magnetic field lines reconnect.

Allowing blood donation from men who had sex with men more than 5 years ago: a model to evaluate the impact on transfusion safety in Canada.

Canada now allows donations from men who had sex with men (MSM) if their last sexual contact with a man was more than 5 years ago. We modelled the impact of this policy on supply and safety. Approximately 4500 new donors will be added and assuming compliance to the new policy remains unchanged, the worst-case scenario predicts the introduction of one HIV-contaminated unit in the inventory every 1072 years. This change will entail negligible additional HIV risk to recipients. A five-year deferral will also protect recipients against the theoretical concern that MSM may represent a group at higher risk of sexually transmitted, emerging blood borne pathogens.

Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease.

Calcineurin-inhibitor refractory bronchiolitis obliterans (BO) represents the leading cause of late graft failure after lung transplantation. T helper (Th)2 and Th17 lymphocytes have been associated with BO development. Taking advantage of a fully allogeneic trachea transplantation model in mice, we addressed the pathogenicity of Th cells in obliterative airway disease (OAD) occurring in cyclosporine A (CsA)-treated recipients. We found that CsA prevented CD8(+) T cell infiltration into the graft and downregulated the Th1 response but affected neither Th2 nor Th17 responses in vivo. In secondary mixed lymphocyte cultures, CsA dramatically decreased donor-specific IFN-γ production, enhanced IL-17 production and did not affect IL-13. As CD4(+) depletion efficiently prevented OAD in CsA-treated recipients, we further explored the role of Th2 and Th17 immunity in vivo. Although IL-4 and IL-17 deficient untreated mice developed an OAD comparable to wild-type recipients, a single cytokine deficiency afforded significant protection in CsA-treated recipients. In conclusion, CsA treatment unbalances T helper alloreactivity and favors Th2 and Th17 as coexisting pathways mediating chronic rejection of heterotopic tracheal allografts.

The epidemiology of human T-cell lymphotropic virus types I and II in Canadian blood donors.

OBJECTIVES: Blood donors in Canada have been tested for Human T-Cell Lymphotropic Virus (HTLV) since 1990. We report the epidemiology, risk factors and lookback/traceback of HTLV-positive donors/recipients. METHODS: The annual HTLV rate was calculated from 1990 to 2010. Residual risk was estimated as the product of incidence and window period. Twenty-nine HTLV-positive donors and 116 matched controls (ratio 1 : 4) were interviewed about risk factors. For HTLV-positive donations, lookback investigations involved identification of all previous donations, and attempting to locate and test recipients. Traceback was initiated when transfusion transmission was queried for HTLV-positive blood recipients. All donors of products that the recipient received were identified, with an attempt to locate and test them. RESULTS: The HTLV rate decreased from 9.35 per 100,000 donations in 1990 to 1.11 in 2010. The residual risk of infection was 1 in 7.6 million donations. In logistic regression birth overseas (OR 18.7), history of sexually transmitted diseases (OR 32.9), sex with unknown background (OR 5.4) and blood transfusion (OR 8.9) were significant predictors. In the lookback study, of 109 HTLV-positive donors, 508 components were transfused, of whom 147 recipients were tested and 18 (12%) were positive. All were transfused prior to the implementation of donor testing. Twenty-three traceback investigations were requested involving 324 transfused untested products,of whom 219 (67.6%) of donors were tested and 13 (6%) were positive for HTLV. CONCLUSIONS: With testing of the blood supply, the risk from HTLV is very low and while most HTLV-positive donors have risk factors, deferrable risk is rare.

Identifying D-positive donors using a second automated testing platform.

Because of the variability of D expression, one method may be inadequate to correctly classify donors with variant RHD alleles. We evaluated the use of a solid -phase automated platform (ImmucorGamma Galileo) to confirm D- test results obtained on first-time donors on the Beckman Coulter PK7300 automated microplate test system. Samples with discordant results were analyzed by serologic tube methods, RHD genotyping using the BLOODchip platform (Progenika) and, if necessary, sequencing. We estimated the number of cases of alloimmunization in women younger than 50 years likelyto be prevented by the addition of Galileo testing. From May 2011 to May 2012, 910,220 donor samples were tested; 15,441 were first-time donors with concordant D- results. Five donors tested D- on the PK7300 and weak D+ on the Galileo; one was found to be a false positive on further testing. On manual testing, the other four donors had positive indirect antiglobulin test results with one to three of the antisera used and were C+. On BLOODchip testing, two donors were classified as D+, and two were assigned a "no call". D variants included weak D type 67, weak D type 9, and two novel variants. Approximately 10 percent of D- units are transfused to women younger that 50 years. Assuming an alloimmunization rate of 30 percent, use of the Galileo would prevent approximately one alloimmunization every 5 to 6 years in this patient group. We conclude that the yield of preventing alloimmunization in this population by adding a second automated seologic testing platform is very low.

Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect.

We have developed a model of gene therapy for cystic fibrosis (CF) lung disease, based on growth of human CF bronchial xenografts in nu/nu mice. We now report an evaluation of the primary abnormalities in CF lung epithelia--defective Cl secretion and Na hyperabsorption--in xenografts following adenovirus-mediated gene transfer. In vivo infection of CF xenografts with a cystic fibrosis transmembrane regulator (CFTR) recombinant adenovirus, at a multiplicity of infection equal to 100, was sufficient to reconstitute near normal levels of cAMP-stimulated Cl transport, despite transducing only 5% of cells in the pseudostratified epithelium. Correction in sodium hyperabsorption was partial and variable. These experiments define aspects of adenovirus-mediated gene therapy relevant to CF protocols based on intrapulmonary genetic reconstitution.

Th17 alloimmunity prevents neonatal establishment of lymphoid chimerism in IL-4-deprived mice.

Immune responses in newborn mice are known to be biased toward the helper type 2 phenotype. This may account for their propensity to develop tolerance. Herein, we evaluated the effects of IL-4 deprivation on CD4(+) T-cell activities elicited by neonatal exposure to allogeneic spleen cells. We showed that chimerism, Th2-type polarization and pathology, as well as skin allograft acceptance were inhibited in BALB/c mice immunized at birth with (A/J x BALB/c) F(1) spleen cells upon in vivo IL-4 neutralization. While IL-4 neutralization inhibited the development of Th2 cells in this model, it led to the accumulation of IL-17A, IL-17F, IL-22, IL-6 and RORγt mRNA in the spleen or graft tissues. Moreover, IL-4 deprivation led to the differentiation of donor-specific Th17 cells with a concomitant Th1 response characterized by IFN-γ production. The Th17-type response emerging in IL-4-deprived mice was found to mediate both intragraft neutrophil infiltration and the abrogation of B-cell chimerism. Neutralization of this Th17 response failed however to restore functional skin graft acceptance. Collectively, our observations indicate that the neonatal Th2 response opposes the development of Th17 cells, and that Th17 cells are responsible for controlling lymphoid chimerism in mice neonatally injected with semiallogeneic cells.

Quantum interference of single photons from remote nitrogen-vacancy centers in diamond.

We demonstrate quantum interference between indistinguishable photons emitted by two nitrogen-vacancy centers in distinct diamond samples separated by two meters. Macroscopic solid immersion lenses are used to enhance photon collection efficiency. Quantum interference is verified by measuring a value of the second-order cross-correlation function g((2))(0)=0.35±0.04<0.5. In addition, optical transition frequencies of two separated nitrogen-vacancy centers are tuned into resonance with each other by applying external electric fields. An extension of the present approach to generate entanglement of remote solid-state qubits is discussed.