Biology subjects

Jansen, S.

Publications and source records attributed to Jansen, S..

At least 37 records · Page 2Linked to original sources

bioRxiv2023

Functional copy number variation in SQUALENE EPOXIDASE-LIKE genes affects photosystem II efficiency in Arabidopsis

In this study, we found a single quantitative trait locus for photosystem II efficiency ({Phi}PSII) in the Arabidopsis Ler-0 x Col-0 recombinant inbred line population. This locus on chromosome 5 is caused by genetic variation in a cluster of tandemly repeated SQUALENE EPOXIDASE-LIKE (SQE-like) genes, with unknown function. We show the QTL is caused by variation in the SQE5, SQE6 and SQE7 genes affecting {Phi}PSII in a dose-dependent manner, due to a combination of functional copies. Col-0 carries only one functional copy, SQE5, while Ler-0 carries functional copies of SQE6 and SQE7. Overexpression of a functional copy of SQE6 enhances {Phi}PSII to exceed that of the Ler-0 parent in Arabidopsis, but does not affect {Phi}PSII in tobacco. Phylogenetic analysis of the SQE and SQE-likes in 135 plant species revealed that the SQE-likes are evolutionary confined to two sister families, the Cleomaceae and Brassicaceae, and diversified independently. The tandem cluster of four SQE-like genes in Arabidopsis is likely the result of two recent gene duplication events, one generating SQE5 from SQE4, the next one generating SQE6 and SQE7 from SQE5. The involvement of SQE-like genes in photosynthesis will open up new avenues to determine the function of these novel genes.

plant biology↗

bioRxiv2023

SOD1 is a synthetic lethal target in PPM1D-mutant leukemia cells

The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacologic target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our results demonstrate the protective role of SOD1 against oxidative stress in PPM1D-mutant leukemia cells and highlight a new potential therapeutic strategy against PPM1D-mutant cancers.

cancer biology↗

bioRxiv2023

Xylem sap residue in cut-open conduits can affect gas discharge in pneumatic experiments

O_LIConsiderable progress has been made in understanding the mechanisms of embolism formation based on the pneumatic method, which relies on gas discharge measurements. Here, we test the assumption that cut-open conduits are gas-filled when samples are cut at high water potentials. C_LIO_LIWe performed vulnerability curves (VC) with the Pneumatron and analysed sap extraction from cut-open vessels in Citrus branches, while the optical method was applied as a reference method. VCs of 11 additional angiosperms were analysed to generalise our findings. C_LIO_LIWe found an increase in gas discharge during early stages of dehydration, which affected the VC of Citrus. Xylem sap was not absorbed immediately by surrounding tissue in cut Citrus branches. The gas amount discharged increased until all sap residue was absorbed, which was near the turgor loss point. By analysing the slope of VCs, we could correct pneumatic VC, as evidenced by the strong agreement in embolism resistance between the pneumatic and the optical method. C_LIO_LISince residual sap in cut-open conduits of some species could slightly reduce embolism resistance in some species, we propose to apply an easy correction for this novel artefact. Automated measurements with a Pneumatron are also required because of its high time resolution. C_LI

plant biology↗

bioRxiv2023

IST1 regulates select endosomal recycling pathways

ESCRTs (Endosomal Sorting Complex Required for Transport) are a modular set of protein complexes with membrane remodeling activities that include the formation and release of intralumenal vesicles (ILVs) to generate multivesicular endosomes. While most of the 12 ESCRT-III proteins are known to play roles in ILV formation, IST1 has been associated with a wider range of endosomal remodeling events. Here, we extend previous studies of IST1 function in endosomal trafficking and confirm that IST1, along with its binding partner CHMP1B, contributes to scission of early endosomal carriers. Depleting IST1 impaired delivery of transferrin receptor from early/sorting endosomes to the endocytic recycling compartment and instead increased its rapid recycling to the plasma membrane via peripheral endosomes enriched in the clathrin adaptor AP-1. IST1 is also important for export of mannose 6-phosphate receptor from early/sorting endosomes. Examination of IST1 binding partners on endosomes revealed that IST1 interacts with the MIT domain-containing sorting nexin SNX15, a protein previously reported to regulate endosomal recycling. Our kinetic and spatial analyses establish that SNX15 and IST1 occupy a clathrin-containing subdomain on the endosomal perimeter distinct from those previously implicated in cargo retrieval or degradation. Using live-cell microscopy we see that SNX15 and CHMP1B alternately recruit IST1 to this subdomain or the base of endosomal tubules. These findings indicate that IST1 contributes to a subset of recycling pathways from the early/sorting endosome. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/551359v2_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@14c2658org.highwire.dtl.DTLVardef@699063org.highwire.dtl.DTLVardef@867084org.highwire.dtl.DTLVardef@44f7b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2023

Gas diffusion kinetics drive embolism spread in angiosperm xylem: evidence from flow-centrifuge experiments and modelling

Understanding xylem embolism formation is challenging due to dynamic changes and multiphase interactions in conduits. If embolism spread involves gas movement in xylem, we hypothesise that it is affected by time. We measured hydraulic conductivity (Kh) in flow-centrifuge experiments over one hour at a given pressure and temperature for stem samples of three angiosperm species. Temporal changes in Kh at 5, 22, and 35{degrees}C, and at various pressures were compared to modelled gas pressure changes in a recently embolised vessel in the centre of a centrifuge sample. Temporal changes in Kh at 22{degrees}C showed maximum relative increases between 6% and 40%, and maximum decreases between 41% and 61% at low and high centrifugal speed, respectively. Logarithmic changes in Kh were species-specific, and most pronounced during the first 15 minutes. Embolism formation started near the edges of centrifuge samples and gradually increased at the centre. Moreover, measured decreases in Kh strongly correlated with modelled increases in gas concentration in a recently embolised vessel. Although embolism is mostly pressure-driven, our experimental and modelled data indicate that time, conduit characteristics, and temperature are involved due to their role in gas diffusion. Gas diffusion, however, does not cover the entire process of embolism spread.

plant biology↗

bioRxiv2023

Lianas in tropical dry forests have higher embolism resistance but similar hydraulic efficiency than lianas in rainforests

Lianas are increasing in relative abundance and biomass, mainly in seasonally dry forests, but it is unclear if this is associated with their hydraulic strategy. Here, we ask whether liana of seasonally dry forests are safer and more efficient in water transport than those of rainforest, which could explain liana distribution patterns and their recent increases. We measured hydraulic traits on five pairs of congeneric liana species (tribe Bignonieae) on one seasonal dry Atlantic forest and one Amazon rainforest. The predawn and minimum water potential, and the water potential at which 50% of the maximum gas amount was discharged were, on average, more negative in the liana species of the seasonal forest. However, these patterns were not constant at the genus level. The positive hydraulic safety margins and hydraulic efficiency were similar among species congeners across sites. The Bignonieae lianas studied likely experience equally low levels of embolism during drought, and maintain a high conductive capacity with efficient use of xylem space, which may favor survival and growth across tropical forests. The likely evolutionary convergence of high hydraulic safety associated with the opportunistic strategy of rapid growth, especially in disturbed areas can favor the abundant liana species in seasonal forests. HighlightTropical forest liana species have high hydraulic efficiency and high interspecific variability in hydraulic safety. Despite this variability, some seasonal forest liana species have greater hydraulic safety than rainforest lianas, indicating an evolutionary convergence across lineages.

plant biology↗

bioRxiv2022

Biodistribution and Environmental Safety of a Live-attenuated YF17D-vectored SARS-CoV-2 Vaccine Candidate

New platforms are urgently needed for the design of novel prophylactic vaccines and advanced immune therapies. Live-attenuated yellow fever vaccine YF17D serves as vector for several licensed vaccines and platform for novel vaccine candidates. Based on YF17D, we developed YF-S0 as exceptionally potent COVID-19 vaccine candidate. However, use of such live RNA virus vaccines raises safety concerns, i.e., adverse events linked to original YF17D (yellow fever vaccine-associated neurotropic; YEL-AND, and viscerotropic disease; YEL-AVD). In this study, we investigated the biodistribution and shedding of YF-S0 in hamsters. Likewise, we introduced hamsters deficient in STAT2 signaling as new preclinical model of YEL-AND/AVD. Compared to parental YF17D, YF-S0 showed an improved safety with limited dissemination to brain and visceral tissues, absent or low viremia, and no shedding of infectious virus. Considering yellow fever virus is transmitted by Aedes mosquitoes, any inadvertent exposure to the live recombinant vector via mosquito bites is to be excluded. The transmission risk of YF-S0 was hence evaluated in comparison to readily transmitting YFV-Asibi strain and non-transmitting YF17D vaccine, with no evidence for productive infection of vector mosquitoes. The overall favorable safety profile of YF-S0 is expected to translate to other novel vaccines that are based on the same YF17D platform.

microbiology↗

bioRxiv2022

Dynamic changes in gas solubility of xylem sap reiterate the enigma of plant water transport under negative pressure

Despite a long research history, we do not fully understand why plants are able to transport xylem sap under negative pressure without constant failure. Microbubble formation via direct gas entry is assumed to cause hydraulic failure, while the concentration of gas dissolved in xylem sap is traditionally supposed to be constant, following Henrys law. Here, the concentration of soluble gas in xylem sap was estimated in vivo using well-watered Citrus plants under varying levels of air temperature and photoperiodic exposure, and compared to modelled data. The gas concentration in xylem sap showed non-equilibrium curves, with a minimum over- or undersaturation of 5% compared to gas solubility based on Henrys law. A similar diurnal pattern was obtained from the gas concentration in the cut-open conduits and discharge tube, and oversolubility was strongly associated with decreasing xylem water potentials during transpiration. Although our model did not explain the daily changes in gas solubility for an anisobaric situation, oversolubility characterises nanoconfined liquids, such as sap inside cell walls. Thus, plants are able to transport sap under negative pressure with relatively high amounts of dissolved gas, providing them with a buffering capacity to prevent hydraulic failure, despite diurnal changes in pressure and temperature.

plant biology↗

bioRxiv2021

Polar lipids are linked to nanoparticles in xylem sap of temperate angiosperm species

Xylem sap of angiosperm species has been found to include low concentrations of polar lipids and nanoparticles, including surfactant-coated nanobubbles. Although the nanoparticles have been suggested to consist of polar lipids, no attempt has been made to determine if nanoparticle and lipid concentrations are related. Here, we examined concentrations of nanoparticles and lipids in xylem sap and contamination control samples of six temperate angiosperm species with a NanoSight device and based on mass spectrometry. We found (1) that the concentration of nanoparticles and lipids were both diluted when an increasing amount of sap was extracted, (2) that their concentrations were significantly correlated in three species, (3) that their concentrations were affected by vessel anatomy, and (4) that concentrations of nanoparticles and lipids were very low in contamination-control samples. Moreover, there was little seasonal difference, no freezing-thawing effect on nanoparticles, and little seasonal variation in lipid composition. These findings indicate that lipids and nanoparticles are related to each other, and largely do not pass interconduit pit membranes. Further research is needed to examine the formation and stability of nanoparticles in xylem sap in relation to lipid composition, and the complicated interactions among the gas, liquid, and solid phases in xylem conduits.

plant biology↗

bioRxiv2021

A novel small molecule that induces cytotoxicity in lung cancer cells inhibits disulfide reductases GSR and TXNRD1

High-throughput phenotype-based screening of large libraries of novel compounds without known targets can identify small molecules that elicit a desired cellular response, but additional approaches are required to find and characterize their targets and mechanisms of action. Here we show that a compound termed lung cancer screen 3 (LCS3), previously selected for its ability to impair the growth of human lung adenocarcinoma (LUAD) cell lines, but not normal lung cells, induces oxidative stress and activates the NRF2 signaling pathway by generating reactive oxygen species (ROS) in sensitive LUAD cell lines. To identify the target that mediates this effect, we applied thermal proteome profiling (TPP) and uncovered the disulfide reductases GSR and TXNRD1 as LCS3 targets. Through enzymatic assays using purified protein, we confirmed that LCS3 inhibits disulfide reductase activity through a reversible, uncompetitive mechanism. Further, we demonstrate that LCS3-sensitive LUAD cells are correspondingly sensitive to the synergistic inhibition of glutathione and thioredoxin pathways. Lastly, a genome-wide CRISPR knockout screen identified the loss of NQO1 as a mechanism of LCS3 resistance. This work highlights the ability of TPP to uncover targets of small molecules identified by high-throughput screens and demonstrates the potential utility of inhibiting disulfide reductases as a therapeutic strategy for LUAD.

cancer biology↗

bioRxiv2021

Accuracy of the pneumatic method for estimating xylem vulnerability to embolism in temperate diffuse-porous tree species

O_LIThe increasing frequency of global change-type droughts has created a need for fast, accurate and widely applicable techniques for estimating xylem embolism resistance to improve forecasts of future forest changes. C_LIO_LIWe used data from 12 diffuse-porous temperate tree species covering a wide range of xylem safety to compare the pneumatic and flow-centrifuge method for constructing xylem vulnerability curves. We evaluated the agreement between parameters estimated with both methods and the sensitivity of pneumatic measurements to the measurement duration. C_LIO_LIThe agreement between xylem water potentials at 50% air discharged (PAD) estimated with the Pneumatron and 50% loss of hydraulic conductivity (PLC) estimated with the flow-centrifuge method was high (mean signed deviation: 0.12 MPa, Pearson correlation: 0.96 after 15 sec of gas extraction). However, the relation between the estimated slopes was more variable, resulting in lower agreement in xylem water potential at 12% and 88% PAD/PLC. All parameters were sensitive to the duration of the pneumatic measurement, with highest overall agreement between methods after 16 sec. C_LIO_LIWe conclude that, if applied correctly, the pneumatic method enables fast and inexpensive estimations of embolism resistance for a wide range of temperate, diffuse-porous species, which makes it attractive for predicting plant performance under climate change. C_LI

plant biology↗

bioRxiv2021

A user manual to measure gas diffusion kinetics in plants: Pneumatron construction, operation and data analysis

The Pneumatron device presented measures gas diffusion kinetics in the xylem of plants. The device provides an easy, low-cost, and powerful tool for research on plant water relations. Here, we describe in detail how to construct and operate this device to estimate xylem vulnerability to embolism, and how to analyse pneumatic data. Simple and more elaborated ways of constructing a Pneumatron are shown, either using wires, a breadboard, or a printed circuit board. The instrument is based on an open-source hardware and software system, which allows users to operate it in an automated or semi-automated way. A step-by-step manual and a troubleshooting section are provided. An excel spreadsheet and an R-script are also presented for fast and easy data analysis. This manual should help new users to avoid common mistakes, especially regarding stable measurements of the minimum and maximum amount of gas that can be discharged from xylem tissue.

plant biology↗

bioRxiv2021

A Unit Pipe Pneumatic model to simulate gas kinetics during measurements of embolism in excised angiosperm xylem

O_LIThe Pneumatic method has been introduced to quantify embolism resistance in plant xylem of various organs. Despite striking similarity in vulnerability curves between the Pneumatic and hydraulic methods, a modeling approach is highly needed to demonstrate that xylem embolism resistance can be accurately quantified based on gas diffusion kinetics. C_LIO_LIA Unit Pipe Pneumatic (UPPn) model was developed to estimate gas diffusion from intact conduits, which were axially interconnected by interconduit pit membranes. The physical laws used included Ficks law for diffusion, Henrys law for gas concentration partitioning between liquid and gas phases at equilibrium, and the ideal gas law. C_LIO_LIThe UPPn model showed that 91% of the extracted gas came from the first two series of embolized, intact conduits, and only 9% from the aqueous phase after 15 s of simulation. Embolism resistance measured with a Pneumatic apparatus was systematically overestimated by 2 to 17%, corresponding to a typical measuring error of 0.11 MPa for P50 (the water potential equivalent to 50% of the maximum amount of gas extracted). C_LIO_LIBecause results from the UPPn model are supported by experimental evidence, there is a good theoretical and experimental basis for applying the pneumatic method to research on embolism resistance of angiosperms. C_LI

plant biology↗

bioRxiv2020

Quaternary climate change explains global patterns of tree beta-diversity

Both historical and contemporary environmental conditions determine present biodiversity patterns, but their relative importance is not well understood. One way to disentangle their relative effects is to assess how different dimensions of beta-diversity relate to past climatic changes, i.e., taxonomic, phylogenetic and functional compositional dissimilarity, and their components generated by replacement of species, lineages and traits (turnover) and richness changes (nestedness). Here, we quantify global patterns of each of these aspects of beta-diversity among neighboring sites for angiosperm trees using the most extensive global database of tree species-distributions (43,635 species). We found that temperature change since the Last Glacial Maximum (LGM) was the major influence on both turnover and nestedness components of beta-diversity, with a negative correlation to turnover and a positive correlation to nestedness. Moreover, phylogenetic and functional nestedness was higher than expected from taxonomic beta-diversity in regions that experienced large temperature changes since the LGM. This pattern reflects relatively greater losses of phylogenetic and functional diversity in species-poor assemblages, possibly caused by phylogenetically and functionally selective species extinction and recolonization during glacial-interglacial oscillations. Our results send a strong warning that rapid anthropogenic climate change is likely to result in a long-lasting phylogenetic and functional compositional simplification, potentially impairing forest ecosystem functioning.

ecology↗

bioRxiv2020

Minding The Gap: Range Size And Economic Use Drive Functional Trait Data Shortfall In The Atlantic Forest

Biodiversity shortfalls are knowledge gaps that may result from uneven sampling through time and space and human interest biases. Gaps in data of functional traits of species may add uncertainty in functional diversity and structure measures and hinder inference on ecosystem functioning and ecosystem services, with negative implications for conservation and restoration practices, such as in Atlantic Forest hotspot. Here we investigate which are the potential drivers of trait data gaps and where geographically they are in the Atlantic Forest. We quantified trait gaps for four key plant functional traits of 2335 trees species, and evaluated which factors drive trait gap at the species and at the geographical level. At the species level, we found larger trait gaps for small-ranged and with no economic use. At the geographical level, we found larger gaps at the Atlantic Forest east coast. Trait gaps were higher away from urban areas, and among species with smaller mean range size and smaller mean economic use of wood, and smaller near protected areas. Efforts on reducing trait gaps of small-ranged and of species with economic use of wood can further advance theory-driven studies and improve knowledge coverage

ecology↗

bioRxiv2020

Abundant circular RNA expression in terminal myeloid differentiation does not correlate with frequent circRNA translation, or with circRNA-mediated translation regulation

Each day, about 1012 erythrocytes and platelets are released into the blood stream. This substantial output from hematopoietic stem cells is tightly regulated by transcriptional and epigenetic factors. Whether and how circular RNAs (circRNAs) contribute to the differentiation and/or identity of hematopoietic cells is to date not known. We recently reported that erythrocytes and platelets contain the highest levels and numbers of circRNAs amongst hematopoietic cells. Here, we provide the first detailed analysis of circRNA expression during erythroid and megakaryoid differentiation. CircRNA expression not only significantly increased upon enucleation, but also had limited overlap between progenitor cells and mature cells, suggesting that circRNA expression stems from regulated processes rather than resulting from mere accumulation. To study circRNA function in hematopoiesis, we first compared the expression levels of circRNAs with the translation efficiency of their mRNA-counterpart. We found that only 1 out of 2531 (0.04%) circRNAs associated with mRNA-translation regulation. Furthermore, irrespective of 1000s of identified putative open reading frames, deep ribosome-footprinting sequencing and mass spectrometry analysis provided little evidence for translation of endogenously expressed circRNAs. In conclusion, circRNAs alter their expression profile during terminal hematopoietic differentiation, yet their contribution to regulate cellular processes remains enigmatic.

molecular biology↗

bioRxiv2020

Pore constrictions in intervessel pit membranes reduce the risk of embolism spreading in angiosperm xylem

O_LIEmbolism spreading in angiosperm xylem occurs via mesoporous pit membranes between vessels. Here, we investigate how the size of pore constrictions in pit membranes is related to pit membrane thickness and embolism resistance. C_LIO_LIIn three models, pit membranes are modelled as multiple layers to investigate how pit membrane thickness and the number of intervessel pits per vessel determine pore constriction sizes, the probability of encountering large pores, and air-seeding. These estimations were complemented by measurements of pit membrane thickness, embolism resistance, and number of intervessel pits per vessel (n = 31, 31, and 20 species, respectively). C_LIO_LIConstriction sizes in pores decreased with increasing pit membrane thickness, which agreed with the measured relationship between pit membrane thickness and embolism resistance. The number of pits per vessel affected constriction size and embolism resistance much less than pit membrane thickness. A strong relationship between estimated air-seeding pressures and measured embolism resistance was observed. C_LIO_LIPore constrictions provide a mechanistic explanation why pit membrane thickness determines embolism resistance, and suggest that hydraulic safety can be uncoupled from hydraulic efficiency. Although embolism spreading remains puzzling and encompasses more than pore constriction sizes, angiosperms are unlikely to have leaky pit membranes, which enables tensile transport of water. C_LI

plant biology↗

bioRxiv2020

Identification of TMEM106B as proviral host factor for SARS-CoV-2

The ongoing COVID-19 pandemic is responsible for worldwide economic damage and nearly one million deaths. Potent drugs for the treatment of severe SARS-CoV-2 infections are not yet available. To identify host factors that support coronavirus infection, we performed genome-wide functional genetic screens with SARS-CoV-2 and the common cold virus HCoV-229E in non-transgenic human cells. These screens identified PI3K type 3 as a potential drug target against multiple coronaviruses. We discovered that the lysosomal protein TMEM106B is an important host factor for SARS-CoV-2 infection. Furthermore, we show that TMEM106B is required for replication in multiple human cell lines derived from liver and lung and is expressed in relevant cell types in the human airways. Our results identify new coronavirus host factors that may potentially serve as drug targets against SARS-CoV-2 or to quickly combat future zoonotic coronavirus outbreaks.

microbiology↗