Search bioRxiv⌕ Search

Biology subjects

Johnson, D. M.

Publications and source records attributed to Johnson, D. M..

6 recordsLinked to original sources

Maftivimab monotherapy is effective in a non-human primate model of Bundibugyo virus disease

The 2026 outbreak of Bundibugyo ebolavirus (BDBV) in the Democratic Republic of the Congo and Uganda has created an urgent need for treatments for BDBV disease, yet the only FDA-approved ebolavirus therapeutics, the monoclonal antibody (mAb) cocktail Inmazeb and the mAb Ebanga, are indicated for Zaire ebolavirus (EBOV). Maftivimab (REGN3479), the most potent neutralizing component of Inmazeb, targets ebolavirus species GPs broadly; however, how it engages BDBV GP, whether it neutralizes BDBV-2026, and whether it protects against BDBV disease in vivo are unknown. Here we show that Maftivimab binds to BDBV-2007 GP with high affinity and potently neutralizes pseudoviruses carrying GP from a 2007 reference strain and the 2026 outbreak lineage. Additionally, a cryo-electron microscopy structure of Maftivimab Fab bound to trimeric BDBV-2007 GP superimposes closely on the EBOV GP:Maftivimab complex; importantly, all GP contact residues are conserved between the 2007 and 2026 BDBV sequences. Finally, in cynomolgus macaques challenged with BDBV-2007, a single dose of Maftivimab monotherapy given 7 days after infection, after the onset of clinical disease, rescued 6 of 6 animals, whereas 5 of 6 placebo-treated animals succumbed. These findings demonstrate that Maftivimab neutralizes BDBV, binds to its epitope on BDBV GP and is efficacious in treating established BDBV disease in the macaque model. The data support its evaluation in clinical trials during the ongoing or future outbreak.

immunology↗

The PSInet Plant Water Potential Database: advancing new perspectives on plant water status, traits, and hydraulic processes

Water potential gradients drive water flow within and between soils and plants, and the internal plant water potential controls a wide range of physiological processes including photosynthesis, growth, and mortality. Notwithstanding this clear relevance for many critical aspects of ecosystem function, water potential data have historically been relatively inaccessible and unnetworked. The absence of a centralized repository for plant water potential time series limits our ability to integrate a wealth of ecophysiological information from other networks and from remote sensing. Closing this gap is necessary to address unresolved questions about plant responses to drought and heat stress, and to make confident predictions about plant and ecosystem function in a warming world. Here, we introduce the PSInet database -- a global collection of plant water potential time series from 285 datasets representing 523 species. We present the workflow that guided database development and evaluate its key features. Through a series of preliminary analyses, we then highlight the potential of the PSInet database for applications including: a) advancing plant water use strategy frameworks; b) disentangling the impacts of soil versus atmospheric drought stress; c) assessing the long-held assumption of pre-dawn equilibration of ecosystem water potential; d) understanding the risk of drought-driven mortality; and e) benchmarking remote-sensing data products and land-surface models.

plant biology↗

Synchronous Miocene radiations and geographic-dependent diversification of pantropical Xylopia (Annonaceae)

AimThe evolutionary drivers of hyperdiversity in tropical rain forests are complex and multifaceted. We used the pantropical Xylopia (Annonaceae) genus to address the diversification of rain forest lineages through time, across different regions, and into novel non-rain forest habitats with a comparative phylogenetic approach. LocationGlobal (pantropical) MethodsWe generated a time-calibrated phylogeny of Xylopia using hybrid capture sequence data, including 88% (168/191 spp.) of species within the genus. Diversification analyses were conducted to test for the presence of rate heterogeneity (BAMM, ClaDS, CoMET) and environmental-dependent (RPANDA), geographic-dependent, and habitat dependent (GeoHiSSE) diversification in Xylopia. ResultsSignificant diversification rate heterogeneity was detected along the backbone of the core Xylopia clade, leading to near synchronous radiations across tropical regions globally in the Miocene, with higher diversification rates in Africa, Central America, and Madagascar, and lower rates in Australia + New Guinea. Transitions from rain forest to subhumid habitats led to lower diversification rates, whereas transitions to ultramafic habitats lead to higher rates. Regional diversification models indicate sea-level changes as an important driver for Asian, Australian, Pacific, and Neotropical clades and regional temperature changes as the main diversification driver for an African clade of Xylopia. Main conclusionsOur study shows that despite synchronous radiations across regions, different regional environmental drivers have affected the diversification of Xylopia across tropical regions globally. A noteworthy example includes radiations of all five Malagasy clades c. 7 Ma coinciding with the establishment of heavy seasonal rainfall linked with the Indian monsoon. The diversification dynamics of rain forests are complex and heterogenous, with different clade-dependent and region-dependent environmental drivers.

evolutionary biology↗

The 3D construction of leaves is coordinated with water use efficiency in conifers

O_LIConifers prevail in the canopies of many terrestrial biomes, holding a great ecological and economic importance globally. Current increases in temperature and aridity are imposing high transpirational demands and resulting in conifer mortality. Therefore, identifying leaf structural determinants of water use efficiency is essential in predicting physiological impacts due to environmental variation. C_LIO_LIUsing synchrotron-generated microCT imaging, we extracted leaf volumetric anatomy and stomatal traits in 34 species across conifers with a special focus on Pinus, the richest conifer genus. C_LIO_LIWe show that intrinsic water use efficiency (WUEi) is positively driven by leaf vein volume. Needle-like leaves of Pinus, as opposed to flat leaves or flattened needles of other genera, showed lower mesophyll porosity, decreasing the relative mesophyll volume. This led to increased ratios of stomatal pore number per mesophyll or intercellular airspace volume, which emerged as powerful explanatory variables, predicting both stomatal conductance and WUEi. C_LIO_LIOur results clarify how the three-dimensional organization of tissues within the leaf has a direct impact on plant water use and carbon uptake. By identifying a suit of structural traits that influence important physiological functions, our findings can help to understand how conifers may respond to the pressures exerted by climate change. C_LI

plant biology↗

Root water gates and not changes in root structure provide new insights into plant physiological responses and adaptations to drought, flooding and salinity

The influence of aquaporin (AQP) activity on plant water movement remains unclear, especially in plants subject to unfavorable conditions. We applied a multitiered approach at a range of plant scales to (i) characterize the resistances controlling water transport under drought, flooding and flooding plus salinity conditions; (ii) quantify the respective effects of AQP activity and xylem structure on root (Kroot), stem (Kstem) and leaf (Kleaf) conductances, and (iii) evaluate the impact of AQP-regulated transport capacity on gas exchange. We found that drought, flooding and flooding-salinity reduced Kroot and root AQP activity in Pinus taeda, whereas Kroot of the flood-tolerant Taxodium distichum did not decline under flooding. The extent of the AQP-control of transport efficiency varied among organs and species, ranging from 35%-55% in Kroot to 10%-30% in Kstem and Kleaf. In response to treatments, AQP-mediated inhibition of Kroot rather than changes in xylem acclimation controlled the fluctuations in Kroot. The reduction in stomatal conductance and its sensitivity to vapor pressure deficit were direct responses to decreased whole-plant conductance triggered by lower Kroot and larger resistance belowground. Our results provide new mechanistic and functional insights on plant hydraulics that are essential to quantifying the influences of future stress on ecosystem function.

developmental biology↗

Extracellular SPARC improves cardiomyocyte contraction during health and disease

Secreted protein acidic and rich in cysteine (SPARC) is a non-structural extracellular matrix protein that regulates interactions between the matrix and neighboring cells. In the cardiovascular system, it is expressed by cardiac fibroblasts, endothelial cells, and in lower levels by ventricular cardiomyocytes. SPARC expression levels are increased upon myocardial injury and also during hypertrophy and fibrosis. We have previously shown that SPARC improves cardiac function after myocardial infarction by regulating post-synthetic procollagen processing, however whether SPARC directly affects cardiomyocyte contraction is still unknown. In this study we demonstrate a novel inotropic function for extracellular SPARC in the healthy heart as well as in the diseased state after myocarditis-induced cardiac dysfunction. We demonstrate SPARC presence on the cardiomyocyte membrane where it is co-localized with the integrin-beta1 and the integrin-linked kinase. Moreover, extracellular SPARC directly improves cardiomyocyte cell shortening ex vivo and cardiac function in vivo, both in healthy myocardium and during coxsackie virus-induced cardiac dysfunction. In conclusion, we demonstrate a novel inotropic function for SPARC in the heart, with a potential therapeutic application when myocyte contractile function is diminished such as that caused by a myocarditis-related cardiac injury.

physiology↗