Identifying transcriptional profiles and evaluating prognostic biomarkers of HIV-associated diffuse large B-cell lymphoma from Malawi

Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to HIV and population aging. Diffuse Large B-cell lymphoma (DLBCL), the most common lymphoma in SSA and worldwide, is highly associated with HIV, but molecular studies of HIV-associated DLBCL are scarce globally. We describe profiling of DLBCL from Malawi, aiming to elucidate tumor biology and identify clinically meaningful biomarkers specifically for SSA. Between June 1, 2013 and June 1, 2016, 59 cases of DLBCL (32 HIV+/27 HIV−) enrolled in the Kamuzu Central Hospital Lymphoma Study were characterized, of which 54 (92%) were negative for Epstein–Barr virus. Gene expression profiling (GEP) by whole transcriptome sequencing was performed on the first 36 cases (22 HIV+/14 HIV−). Immunohistochemistry (IHC) and GEP results were compared with published data and correlated to clinical outcome and pathologic features. Unsupervised clustering strongly segregated DLBCL by HIV status (p = 0.0003, Chi-squared test), indicating a marked contribution of HIV to expression phenotype. Pathway analysis identified that HIV-associated tumors were enriched in hypoxia, oxidative stress, and metabolism related gene expression patterns. Cell-of-origin subtype, determined by sequencing and IHC, did not associate with differences in overall survival (OS), while Ki-67 proliferation index ≥80% was associated with inferior OS in HIV+ DLBCL only (p = 0.03) and cMYC/BCL2 co-expression by IHC was negatively prognostic across the entire cohort (p = 0.01). This study provides among the first molecular characterizations of DLBCL from SSA, demonstrates marked gene expression differences by HIV status, and identifies genomic and immunophenotypic characteristics that can inform future basic and clinical investigations

Observation of Two New N* Peaks in J/psi -> ppi−nˉp pi^- \bar n and pˉπ+n\bar p\pi^+n Decays

The $\pi N$ system in decays of $J/\psi\to\bar NN\pi$ is limited to be isospin 1/2 by isospin conservation. This provides a big advantage in studying $N^*\to \pi N$ compared with $\pi N$ and $\gamma N$ experiments which mix isospin 1/2 and 3/2 for the $\pi N$ system. Using 58 million $J/\psi$ decays collected with the Beijing Electron Positron Collider, more than 100 thousand $J/\psi \to p \pi^- \bar n + c.c.$ events are obtained. Besides two well known $N^*$ peaks at 1500 MeV and 1670 MeV, there are two new, clear $N^*$ peaks in the $p\pi$ invariant mass spectrum around 1360 MeV and 2030 MeV. They are the first direct observation of the $N^*(1440)$ peak and a long-sought "missing" $N^*$ peak above 2 GeV in the $\pi N$ invariant mass spectrum. A simple Breit-Wigner fit gives the mass and width for the $N^*(1440)$ peak as $1358\pm 6 \pm 16$ MeV and $179\pm 26\pm 50$ MeV, and for the new $N^*$ peak above 2 GeV as $2068\pm 3^{+15}_{-40}$ MeV and $165\pm 14\pm 40$ MeV, respectively

Search for Invisible Decays of η\eta and η′\eta^\prime in J/ψ→ϕηJ/\psi \to \phi\eta and ϕη′\phi \eta^\prime

Using a data sample of $58\times 10^6$ $J/\psi$ decays collected with the BES II detector at the BEPC, searches for invisible decays of $\eta$ and $\eta^\prime$ in $J/\psi$ to $\phi\eta$ and $\phi\eta^\prime$ are performed. The $\phi$ signals, which are reconstructed in $K^+K^-$ final states, are used to tag the $\eta$ and $\eta^\prime$ decays. No signals are found for the invisible decays of either $\eta$ or $\eta^\prime$, and upper limits at the 90% confidence level are determined to be $1.65 \times 10^{-3}$ for the ratio $\frac{B(\eta\to \text{invisible})}{B(\eta\to\gamma\gamma)}$ and $6.69\times 10^{-2}$ for $\frac{B(\eta^\prime\to \text{invisible})}{B(\eta^\prime\to\gamma\gamma)}$. These are the first searches for $\eta$ and $\eta^\prime$ decays into invisible final states.Comment: 5 pages, 4 figures; Added references, Corrected typo

PD1-based DNA vaccine amplifies HIV-1 GAG-specific CD8+ T cells in mice

Viral vector-based vaccines that induce protective CD8+ T cell immunity can prevent or control pathogenic SIV infections, but issues of preexisting immunity and safety have impeded their implementation in HIV-1. Here, we report the development of what we believe to be a novel antigen-targeting DNA vaccine strategy that exploits the binding of programmed death-1 (PD1) to its ligands expressed on dendritic cells (DCs) by fusing soluble PD1 with HIV-1 GAG p24 antigen. As compared with non-DC-targeting vaccines, intramuscular immunization via electroporation (EP) of the fusion DNA in mice elicited consistently high frequencies of GAG-specific, broadly reactive, polyfunctional, long-lived, and cytotoxic CD8+ T cells and robust anti-GAG antibody titers. Vaccination conferred remarkable protection against mucosal challenge with vaccinia GAG viruses. Soluble PD1-based vaccination potentiated CD8+ T cell responses by enhancing antigen binding and uptake in DCs and activation in the draining lymph node. It also increased IL-12-producing DCs and engaged antigen cross-presentation when compared with anti-DEC205 antibody-mediated DC targeting. The high frequency of durable and protective GAG-specific CD8+ T cell immunity induced by soluble PD1-based vaccination suggests that PD1-based DNA vaccines could potentially be used against HIV-1 and other pathogens.published_or_final_versio

PhP.B enhanced adeno-associated virus mediated-expression following systemic delivery or direct brain administration

Of the adeno-associated viruses (AAVs), AAV9 is known for its capability to cross the blood-brain barrier (BBB) and can, therefore, be used as a noninvasive method to target the central nervous system. Furthermore, the addition of the peptide PhP.B to AAV9 increases its transduction across the BBB by 40-fold. Another neurotropic serotype, AAV5, has been shown as a gene therapeutic delivery vehicle to ameliorate several neurodegenerative diseases in preclinical models, but its administration requires invasive surgery. In this study, AAV9-PhP.B and AAV5-PhP.B were designed and produced in an insect cell-based system. To AAV9, the PhP.B peptide TLAVPFK was added, whereas in AAV5-PhP.B (AQTLAVPFKAQAQ), with AQ-AQAQ sequences used to swap with the corresponding sequence of AAV5. The addition of PhP.B to AAV5 did not affect its capacity to cross the mouse BBB, while increased transduction of liver tissue was observed. Then, intravenous (IV) and intrastriatal (IStr) delivery of AAV9-PhP.B and AAV5 were compared. For AAV9-PhP.B, similar transduction and expression levels were achieved in the striatum and cortex, irrespective of the delivery method used. IStr administration of AAV5 resulted in significantly higher amounts of vector DNA and therapeutic miRNA in the target regions such as striatum and cortex when compared with an IV administration of AAV9-PhP.B. These results illustrate the challenge in developing a vector that can be delivered noninvasively while achieving a transduction level similar to that of direct administration of AAV5. Thus, for therapeutic miRNA delivery with high local expression requirements, intraparenchymal delivery of AAV5 is preferred, whereas a humanized AAV9-PhP.B may be useful when widespread brain (and peripheral) transduction is needed.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Interpretation of electrical conductivity measurements from ceramic suction cups, wetting front detectors and ECH2O-TE sensors

Electrical conductivity (EC) measurements are often used to identify and address soil salinity issues in irrigated cropping systems. In this study, measurements of soil solution EC (EC-sol) collected in ceramic suction cups (SCs), wetting front EC (EC-wf) collected in Fullstop wetting front detectors (WFDs) and soil bulk EC (EC-bulk) measurements made using ECH2O-TE sensors and converted to EC-sol, were compared. As a result of different methods of measurement and different components of soil waterflow being sampled, variations in EC measurement between SCs and WFDs were observed. EC-sol was usually higher than EC-wf, as expected for this system, due to incomplete mixing between the draining and resident soil water during infiltration. For periods of high solute leaching, however, the opposite can occur, indicating that WFDs are sampling when solutes are first mobilised at the beginning of the leaching event. The ECH2O-TE sensors were less effective in measuring the short-term EC dynamics but were able to detect general changes in soil salinity. This could reflect difficulties estimating soil EC-sol from measured EC-bulk, especially at low soil water contents. Each of these instruments show good potential for application to guide salinity management practices, but a more detailed study on a range of soils subjected to different watering regimes is needed to further improve interpretation of EC measurements and their application.The Water Research Commission (Project 1574), the National Research Foundation, the Cooperative Research Centre for Irrigation Futures and CSIRO.http://www.plantandsoil.co.zanf201

Modelling nitrogen leaching : are we getting the right answer for the right reason?

The complexities and challenges in quantifying N leaching have led to development of a range of measurement and modelling techniques, but none are widely applied. Observations that N moves more slowly than water through the soil profile has resulted in different approaches being used to simulate impeded N movement in crop models: (i) by accounting for nitrate NO−3 adsorption to the soil, (ii) by considering incomplete mixing between resident and draining soil water fractions or (iii) a combination of both.We compare and discuss strengths and weaknesses of these approaches. Our inability to directly measure model parameters (especially with regards to simulating N dynamics), and the risk of compensating errors during model testing and calibration, often results in low confidence in simulated N leaching. We caution that our current ability to simulate N leaching is in most cases not yet well enough developed for reliable and accurate predictions. We recommend a more strategic approach involving better linking measurement and modelling to improve understanding of the critical soil processes that control N leaching as one way of further improving our understanding and quantification of N leaching.http://www.elsevier.com/locate/agwathb201

Direct Measurements of the Branching Fractions for D0→K−e+νeD^0 \to K^-e^+\nu_e and D0→π−e+νeD^0 \to \pi^-e^+\nu_e and Determinations of the Form Factors f+K(0)f_{+}^{K}(0) and f+π(0)f^{\pi}_{+}(0)

The absolute branching fractions for the decays $D^0 \to K^-e ^+\nu_e$ and $D^0 \to \pi^-e^+\nu_e$ are determined using $7584\pm 198 \pm 341$ singly tagged $\bar D^0$ sample from the data collected around 3.773 GeV with the BES-II detector at the BEPC. In the system recoiling against the singly tagged $\bar D^0$ meson, $104.0\pm 10.9$ events for $D^0 \to K^-e ^+\nu_e$ and $9.0 \pm 3.6$ events for $D^0 \to \pi^-e^+\nu_e$ decays are observed. Those yield the absolute branching fractions to be $BF(D^0 \to K^-e^+\nu_e)=(3.82 \pm 0.40\pm 0.27)$ and $BF(D^0 \to \pi^-e^+\nu_e)=(0.33 \pm 0.13\pm 0.03)$. The vector form factors are determined to be $|f^K_+(0)| = 0.78 \pm 0.04 \pm 0.03$ and $|f^{\pi}_+(0)| = 0.73 \pm 0.14 \pm 0.06$. The ratio of the two form factors is measured to be $|f^{\pi}_+(0)/f^K_+(0)|= 0.93 \pm 0.19 \pm 0.07$.Comment: 6 pages, 5 figure

Measurements of J/psi Decays into 2(pi+pi-)eta and 3(pi+pi-)eta

Based on a sample of 5.8X 10^7 J/psi events taken with the BESII detector, the branching fractions of J/psi--> 2(pi+pi-)eta and J/psi-->3(pi+pi-)eta are measured for the first time to be (2.26+-0.08+-0.27)X10^{-3} and (7.24+-0.96+-1.11)X10^{-4}, respectively.Comment: 11 pages, 6 figure

Study of J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar

The branching ratios and Angular distributions for J/psi decays to Lambda Lambdabar and Sigma0 Sigma0bar are measured using BESII 58 million J/psi.Comment: 11 pages, 5 figure