Aestivation and hypoxia-related events share common silent neuron trafficking processes

10.1186/1471-2202-13-39BMC Neuroscience131-BNME

Pion photoproduction on the nucleon in the quark model

We present a detailed quark-model study of pion photoproduction within the effective Lagrangian approach. Cross sections and single-polarization observables are investigated for the four charge channels, $\gamma p\to \pi^+ n$, $\gamma n\to \pi^- p$, $\gamma p\to \pi^0 p$, and $\gamma n\to \pi^0 n$. Leaving the $\pi N\Delta$ coupling strength to be a free parameter, we obtain a reasonably consistent description of these four channels from threshold to the first resonance region. Within this effective Lagrangian approach, strongly constrainted by the quark model, we consider the issue of double-counting which may occur if additional {\it t}-channel contributions are included.Comment: Revtex, 35 pages, 16 eps figures; version to appear on PR

Vector meson production and nucleon resonance analysis in a coupled-channel approach for energies m_N < sqrt(s) < 2 GeV II: photon-induced results

We present a nucleon resonance analysis by simultaneously considering all pion- and photon-induced experimental data on the final states gamma N, pi N, 2 pi N, eta N, K Lambda, K Sigma, and omega N for energies from the nucleon mass up to sqrt(s) = 2 GeV. In this analysis we find strong evidence for the resonances P_{31}(1750), P_{13}(1900), P_{33}(1920), and D_{13}(1950). The omega N production mechanism is dominated by large P_{11}(1710) and P_{13}(1900) contributions. In this second part we present the results on the photoproduction reactions and the electromagnetic properties of the resonances. The inclusion of all important final states up to sqrt(s) = 2 GeV allows for estimates on the importance of the individual states for the GDH sum rule.Comment: 41 pages, 26 figures, discussion extended, typos corrected, references updated, to appear in Phys. Rev.

Effective Lagrangian Approach to the Theory of Eta Photoproduction in the N∗(1535)N^{*}(1535) Region

We investigate eta photoproduction in the $N^{*}(1535)$ resonance region within the effective Lagrangian approach (ELA), wherein leading contributions to the amplitude at the tree level are taken into account. These include the nucleon Born terms and the leading $t$-channel vector meson exchanges as the non-resonant pieces. In addition, we consider five resonance contributions in the $s$- and $u$- channel; besides the dominant $N^{*}(1535)$, these are: $N^{*}(1440),N^{*}(1520),N^{*}(1650)$ and $N^{*}(1710)$. The amplitudes for the $\pi^\circ$ and the $\eta$ photoproduction near threshold have significant differences, even as they share common contributions, such as those of the nucleon Born terms. Among these differences, the contribution to the $\eta$ photoproduction of the $s$-channel excitation of the $N^{*}(1535)$ is the most significant. We find the off-shell properties of the spin-3/2 resonances to be important in determining the background contributions. Fitting our effective amplitude to the available data base allows us to extract the quantity $\sqrt{\chi \Gamma_\eta} A_{1/2}/\Gamma_T$, characteristic of the photoexcitation of the $N^{*}(1535)$ resonance and its decay into the $\eta$-nucleon channel, of interest to precise tests of hadron models. At the photon point, we determine it to be $(2.2\pm 0.2)\times 10^{-1} GeV^{-1}$ from the old data base, and $(2.2\pm 0.1) \times 10^{-1} GeV^{-1}$ from a combination of old data base and new Bates data. We obtain the helicity amplitude for $N^{*}(1535)\rightarrow \gamma p$ to be $A_{1/2}=(97\pm 7)\times 10^{-3} GeV^{-1/2}$ from the old data base, and $A_{1/2}=(97\pm 6)\times 10^{-3} GeV^{-1/2}$ from the combination of the old data base and new Bates data, compared with the results of the analysis of pion photoproduction yielding $74\pm 11$, in the same units.Comment: 43 pages, RevTeX, 9 figures available upon request, to appear in Phys. Rev.

Modeling the emergence of viral resistance for SARS-CoV-2 during treatment with an anti-spike monoclonal antibody

To mitigate the loss of lives during the COVID-19 pandemic, emergency use authorization was given to several anti-SARS-CoV-2 monoclonal antibody (mAb) therapies for the treatment of mild-to-moderate COVID-19 in patients with a high risk of progressing to severe disease. Monoclonal antibodies used to treat SARS-CoV-2 target the spike protein of the virus and block its ability to enter and infect target cells. Monoclonal antibody therapy can thus accelerate the decline in viral load and lower hospitalization rates among high-risk patients with variants susceptible to mAb therapy. However, viral resistance has been observed, in some cases leading to a transient viral rebound that can be as large as 3-4 orders of magnitude. As mAbs represent a proven treatment choice for SARS-CoV-2 and other viral infections, evaluation of treatment-emergent mAb resistance can help uncover underlying pathobiology of SARS-CoV-2 infection and may also help in the development of the next generation of mAb therapies. Although resistance can be expected, the large rebounds observed are much more difficult to explain. We hypothesize replenishment of target cells is necessary to generate the high transient viral rebound. Thus, we formulated two models with different mechanisms for target cell replenishment (homeostatic proliferation and return from an innate immune response antiviral state) and fit them to data from persons with SARS-CoV-2 treated with a mAb. We showed that both models can explain the emergence of resistant virus associated with high transient viral rebounds. We found that variations in the target cell supply rate and adaptive immunity parameters have a strong impact on the magnitude or observability of the viral rebound associated with the emergence of resistant virus. Both variations in target cell supply rate and adaptive immunity parameters may explain why only some individuals develop observable transient resistant viral rebound. Our study highlights the conditions that can lead to resistance and subsequent viral rebound in mAb treatments during acute infection

Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19

Anti-SARS-CoV-2 monoclonal antibodies are mainstay COVID-19 therapeutics. Safety, antiviral, and clinical efficacy of bamlanivimab were evaluated in the randomized controlled trial ACTIV-2/A5401. Non-hospitalized adults were randomized 1:1 within 10 days of COVID-19 symptoms to bamlanivimab or blinded-placebo in two dose-cohorts (7000 mg, n = 94; 700 mg, n = 223). No differences in bamlanivimab vs placebo were observed in the primary outcomes: proportion with undetectable nasopharyngeal SARS-CoV-2 RNA at days 3, 7, 14, 21, and 28 (risk ratio = 0.82-1.05 for 7000 mg [p(overall) = 0.88] and 0.81-1.21 for 700 mg [p(overall) = 0.49]), time to symptom improvement (median 21 vs 18.5 days [p = 0.97], 7000 mg; 24 vs 20.5 days [p = 0.08], 700 mg), or grade 3+ adverse events. However, bamlanivimab was associated with lower day 3 nasopharyngeal viral levels and faster reductions in inflammatory markers and viral decay by modeling. This study provides evidence of faster reductions in nasopharyngeal SARS-CoV-2 RNA levels but not shorter symptom durations in non-hospitalized adults with early variants of SARS-CoV-2

The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance

In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Health in times of uncertainty in the eastern Mediterranean region, 1990�2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The eastern Mediterranean region is comprised of 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, the United Arab Emirates, and Yemen. Since our Global Burden of Disease Study 2010 (GBD 2010), the region has faced unrest as a result of revolutions, wars, and the so-called Arab uprisings. The objective of this study was to present the burden of diseases, injuries, and risk factors in the eastern Mediterranean region as of 2013. Methods GBD 2013 includes an annual assessment covering 188 countries from 1990 to 2013. The study covers 306 diseases and injuries, 1233 sequelae, and 79 risk factors. Our GBD 2013 analyses included the addition of new data through updated systematic reviews and through the contribution of unpublished data sources from collaborators, an updated version of modelling software, and several improvements in our methods. In this systematic analysis, we use data from GBD 2013 to analyse the burden of disease and injuries in the eastern Mediterranean region specifically. Findings The leading cause of death in the region in 2013 was ischaemic heart disease (90·3 deaths per 100�000 people), which increased by 17·2 since 1990. However, diarrhoeal diseases were the leading cause of death in Somalia (186·7 deaths per 100�000 people) in 2013, which decreased by 26·9 since 1990. The leading cause of disability-adjusted life-years (DALYs) was ischaemic heart disease for males and lower respiratory infection for females. High blood pressure was the leading risk factor for DALYs in 2013, with an increase of 83·3 since 1990. Risk factors for DALYs varied by country. In low-income countries, childhood wasting was the leading cause of DALYs in Afghanistan, Somalia, and Yemen, whereas unsafe sex was the leading cause in Djibouti. Non-communicable risk factors were the leading cause of DALYs in high-income and middle-income countries in the region. DALY risk factors varied by age, with child and maternal malnutrition affecting the younger age groups (aged 28 days to 4 years), whereas high bodyweight and systolic blood pressure affected older people (aged 60�80 years). The proportion of DALYs attributed to high body-mass index increased from 3·7 to 7·5 between 1990 and 2013. Burden of mental health problems and drug use increased. Most increases in DALYs, especially from non-communicable diseases, were due to population growth. The crises in Egypt, Yemen, Libya, and Syria have resulted in a reduction in life expectancy; life expectancy in Syria would have been 5 years higher than that recorded for females and 6 years higher for males had the crisis not occurred. Interpretation Our study shows that the eastern Mediterranean region is going through a crucial health phase. The Arab uprisings and the wars that followed, coupled with ageing and population growth, will have a major impact on the region's health and resources. The region has historically seen improvements in life expectancy and other health indicators, even under stress. However, the current situation will cause deteriorating health conditions for many countries and for many years and will have an impact on the region and the rest of the world. Based on our findings, we call for increased investment in health in the region in addition to reducing the conflicts. Funding Bill & Melinda Gates Foundation. © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY licens