Biology subjects

Bar-On, Y.

Publications and source records attributed to Bar-On, Y..

4 recordsLinked to original sources

bioRxiv2023

Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity

Targeting multiple viral proteins is pivotal for sustained viral suppression. In recent years, several broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed. However, the impact of dual neutralization of these two glycoproteins on the course of infection has not been thoroughly tested. Here we demonstrate that a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase has a dual antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We further show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over antibody combination as it results in an improved neutralization capacity and augmented antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice. These findings suggest that dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.

immunology↗

bioRxiv2022

Anthroponumbers.org: A Quantitative Database Of Human Impacts on Planet Earth

The Human Impacts Database (www.anthroponumbers.org) is a curated searchable resource housing quantitative data relating to the diverse anthropogenic impacts on our planet, with topics ranging from sea level rise, to livestock populations, greenhouse gas emissions, fertilizer use, and beyond. Each entry in the database relates a quantitative value (or a time-series of values) along with clear referencing of the primary source, the method of measurement or estimation, an assessment of uncertainty, links to the underlying data, as well as a permanent identifier called an Human Impacts ID ("HuID"). While there are other databases that house some of these values, they are typically focused on a single topic area like energy usage or greenhouse gas emissions. The Human Impacts Database provides centralized access to quantitative information about the myriad ways in which humans impact the Earth, giving links to more specialized databases for interested readers. Here, we outline the structure of the database and describe our curation procedures. Finally, we use this database to generate a graphical summary of the current state of human impacts on the Earth, illustrating both their numerical values and their dense interconnections. The Bigger PictureOver the last 10,000 years, human activities have transformed the Earth through farming, forestry, mining and industry. The complex results of these activities are now observed and quantified as "human impacts" on Earths atmosphere, oceans, biosphere and geochemistry. While myriad studies have explored facets of human impacts on the planet, they are necessarily technical and often tightly-focused. Thus, finding reliable quantitative information requires a significant investment of time to assess each quantity, its methods of determination, and associated uncertainty. We present the Human Impacts Database (www.anthroponumbers.org), which houses a diverse array of such quantities. We review a subset of these values and how they help build intuition for understanding the Earth-human system. While collation alone does not tell us how to best ameliorate human impacts, we contend that any future plans should be made in light of a quantitative understanding of the interconnected ways in which humans impact the planet.

ecology↗

bioRxiv2022

Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses

Antiretroviral therapy controls but does not cure HIV-1 infection due to a reservoir of rare CD4+ T cells harboring latent proviruses. Little is known about the transcriptional program of latent cells. Here we report a novel strategy to enrich clones of latent cells carrying intact, replication- competent HIV-1 proviruses from blood based on their expression of unique T cell receptors. Latent cell enrichment enabled single cell transcriptomic analysis of 1,050 CD4+ T cells belonging to expanded clones harboring intact HIV-1 proviruses from 6 different individuals. The analysis revealed that most of these cells are T effector memory cells that are enriched for expression of HLA-DR, HLA-DP, CD74, CCL5, Granzymes A and K, cystatin F, LYAR and DUSP2. We conclude that expanded clones of latent cells carrying intact HIV-1 proviruses persist preferentially in a distinct CD4+ T cell population opening new possibilities for eradication. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/482683v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@19e89d2org.highwire.dtl.DTLVardef@16a5685org.highwire.dtl.DTLVardef@563a97org.highwire.dtl.DTLVardef@120a224_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2018

Revisiting tradeoffs in Rubisco kinetic parameters

Rubisco is the most abundant enzyme in the biosphere and one of the best-characterized enzymes. Based on correlations between Rubisco kinetic parameters, it is widely posited that tradeoffs embedded in the catalytic mechanism constrain its specificity and maximum catalytic rate. However, the reasoning that established this view was based on data from {approx}20 organisms. We re-examine these tradeoff models using a dataset from {approx}300 organisms. Most correlations are substantially attenuated, with the inverse relationship between carboxylation kcat and specificity SC/O being a key example. Only one tradeoff model survives in our dataset. In this model, increasing catalytic efficiency (kcat/KM) for carboxylation requires increased catalytic efficiency for the competing oxygenation reaction, evidenced by strong power-law correlation between catalytic efficiencies. Our results imply that Rubisco evolution is constrained primarily by the physicochemical limits of O2/CO2 discrimination, which should reframe efforts to engineer this very central enzyme.

systems biology↗