Biology subjects

Blum, S.

Publications and source records attributed to Blum, S..

6 recordsLinked to original sources

bioRxiv2024

SIRPalpha+ PD-L1+ bone marrow macrophages aid AML growth by modulating T cell function

Acute myeloid leukemia (AML) continues to have a poor prognosis due to its ability to relapse following initial response to chemotherapy. While immunotherapies hold the promise to revolutionize cancer treatment, AML has been particularly challenging to target. It is therefore important to better understand the relationship between AML cells and immune cells within the bone marrow (BM) microenvironment, where this disease grows. Here we focus on non-malignant BM macrophages, and using a combination of intravital microscopy, flow cytometry, transcriptomics and functional analyses we identify a subpopulation of immunomodulatory BM macrophages (IMMs) with a unique profile and function during AML progression. While the majority of macrophages are already being lost at early infiltration, IMMs are locally enriched. They are capable of efferocytosis and support AML growth through inhibition of T cells. Enrichment of IMMs in the BM of patients developing early relapse indicates that future development of interventions that target IMMs development and function may improve AML patients outcome.

cancer biology↗

bioRxiv2021

Real-time audio processing of real-life soundscapes for EEG analysis: ERPs based on natural sound onsets

With smartphone-based mobile electroencephalography (EEG), we can investigate sound perception beyond the lab. To understand sound perception in the real world, we need to relate naturally occurring sounds to EEG data. For this, EEG and audio information need to be synchronized precisely, only then it is possible to capture fast and transient evoked neural responses and relate them to individual sounds. We have developed Android applications (AFEx and Record-a) that allow for the concurrent acquisition of EEG data and audio features, i.e., sound onsets, average signal power (RMS) and power spectral density (PSD) on smartphone. In this paper, we evaluate these apps by computing event-related potentials (ERPs) evoked by everyday sounds. One participant listened to piano notes (played live by a pianist) and to a home-office soundscape. Timing tests showed that the temporal precision of the system is very good. We calculated ERPs to sound onsets and observed the typical P1-N1-P2 complex of auditory processing. Furthermore, we show how to relate information on loudness (RMS) and spectra (PSD) to brain activity. In future studies, we can use this system to study sound processing in everyday life.

neuroscience↗

bioRxiv2021

Inhibition of gibberellin accumulation by water deficiency promotes fast and long-term 'drought avoidance' responses in tomato

Plants reduce transpiration to avoid dehydration during drought episodes by stomatal closure and inhibition of canopy growth. While abscisic acid (ABA) has a primary role in drought avoidance, previous studies suggest that gibberellin (GA), might also be involved. Here we show in tomato (Solanum lycopersicum) that shortage of water inhibited the expression of the GA biosynthesis genes GA20 oxidase1 (GA20ox1) and GA20ox2 and induced the GA-deactivating gene GA2ox7 in leaves and guard cells, resulting in reduced bioactive GA levels. Drought regulation of GA metabolism was mediated by ABA-dependent and independent pathways, and by the transcription factor DEHYDRATION RESPONSIVE ELEMENT BINDING (DREB), TINY1. Mutations in GA20ox1 and GA20ox2 reduced water loss due to the smaller canopy area. On the other hand, loss of GA2ox7 did not affect leaf size, but attenuated stomatal response to water deficiency; during soil dehydration, ga2ox7 plants closed their stomata and reduced transpiration later than WT, suggesting that ga2ox7 stomata are hyposensitive to soil dehydration. Together, the results suggest that drought-induced GA deactivation in guard cells contributes to stomatal closure at the early stages of soil dehydration, whereas inhibition of GA synthesis in leaves promotes mainly the long-term reduction in canopy growth to reduce transpiration area.

molecular biology↗

bioRxiv2021

Cannabinoid signaling promotes the reprogramming of Muller glia into proliferating progenitor cells.

Endocannabinoids (eCB) are lipid-based neurotransmitters that are known to influence synaptic function in the visual system. eCBs are also known to suppress neuroinflammation in different pathological states. However, nothing is known about the roles of the eCB system during reprogramming of Muller glia (MG) into proliferating progenitor-like cells in the retina. Accordingly, we used the chick and mouse model to characterize expression patterns of eCB-related genes and applied pharmacological agents to examine how the eCB system impacts glial reactivity and the capacity of MG to become Muller glia-derived progenitor cells (MGPCs). We probed single cell RNA-seq libraries to identify eCB-related genes and identify cells with dynamic patterns of expression in damaged retinas. MG and inner retinal neurons expressed the eCB receptor CNR1, as well as enzymes involved in eCB metabolism. In the chick, intraocular injections of 2-Arachidonoylglycerol (2-AG) and Anandamide (AEA) potentiated the formation of MGPCs. Consistent with these findings, CNR1-agonists and MGLL-inhibitor promoted reprogramming, whereas CNR1-antagonist and inhibitors of eCB synthesis suppressed reprogramming. Surprisingly, retinal microglia were largely unaffected by increases or decreases in eCB signaling in both chick and mouse models. However, eCB-signaling suppressed the activation of NFkB-reporter in MG in damaged mouse retinas. We conclude that the eCB system in the retina influences the reactivity of MG and is important for regulating glial reactivity and the reprogramming of MG into proliferating MGPCs, but not for regulating the reactivity of immune cells in the retina. Main PointsMuller glia express CNR1 receptor and endocannabinoid synthesis genes. Endocannabinoids after retinal damage promote the formation of Muller glia derived progenitor cells in chick. Endocannabinoids reduce NFkB activity in mouse Muller glia.

molecular biology↗

bioRxiv2019

Grass silica mineralizer (GSM1) protein precipitates silica in sorghum silica cells

O_LISilicon is absorbed by plant roots as silicic acid. The acid moves with the transpiration stream to the shoot, and mineralizes as silica. In grasses, leaf epidermal cells called silica cells deposit silica in most of their volume by unknown mechanism.\nC_LIO_LIUsing bioinformatics tools, we identified a previously uncharacterized protein in sorghum (Sorghum bicolor), which we named Siliplant1 (Slp1). Silica precipitation activity in vitro, expression profile, and activity in precipitating biosilica in vivo were characterized.\nC_LIO_LISlp1 is a basic protein with seven repeat units rich in proline, lysine, and glutamic acid. A short peptide, repeating five times in the protein precipitated silica in vitro at a biologically relevant silicic acid concentration. Raman and NMR spectroscopies showed that the peptide attached the silica through lysine amine groups, forming a mineral-peptide open structure. We found Slp1 expression in immature leaf and inflorescence tissues. In the immature leaf active silicification zone, Slp1 was localized to the cytoplasm or near cell boundaries of silica cells. It was packed in vesicles and secreted to the paramural space. Transient overexpression of Slp1 in sorghum resulted in ectopic silica deposition in all leaf epidermal cell types.\nC_LIO_LIOur results show that Slp1 precipitates silica in sorghum silica cells.\nC_LI

plant biology↗

bioRxiv2017

Genome Graphs

There is increasing recognition that a single, monoploid reference genome is a poor universal reference structure for human genetics, because it represents only a tiny fraction of human variation. Adding this missing variation results in a structure that can be described as a mathematical graph: a genome graph. We demonstrate that, in comparison to the existing reference genome (GRCh38), genome graphs can substantially improve the fractions of reads that map uniquely and perfectly. Furthermore, we show that this fundamental simplification of read mapping transforms the variant calling problem from one in which many non-reference variants must be discovered de-novo to one in which the vast majority of variants are simply re-identified within the graph. Using standard benchmarks as well as a novel reference-free evaluation, we show that a simplistic variant calling procedure on a genome graph can already call variants at least as well as, and in many cases better than, a state-of-the-art method on the linear human reference genome. We anticipate that graph-based references will supplant linear references in humans and in other applications where cohorts of sequenced individuals are available.

bioinformatics↗