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Biology subjects

Zweig, N.

Publications and source records attributed to Zweig, N..

3 recordsLinked to original sources

Lipid signatures and inter-cellular heterogeneity of naive and lipopolysaccharide-stimulated human microglia-like cells

Microglia are non-neuronal cells, which are residing in the central nervous system and are known to play an important role in health and disease. We investigated lipidomic phenotypes of human naive and stimulated microglia-like cells by atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI). With lateral resolutions between 5 m and 1.5 m, we were able to chart lipid compositions of individual cells, enabling to differentiate cell lines and stimulation conditions. This allowed us to reveal local lipid heterogeneities in naive and lipopolysaccharide (LPS)-stimulated cells. We were able to identify individual cells with elevated triglyceride (TG) levels and could show that the number of these TG-enriched cells increased with LPS stimulation as a hallmark for a proinflammatory phenotype. Additionally, observed local abundance alterations of specific phosphatidylinositols (PIs) indicate a cell specific regulation of the PI metabolism.

biochemistry↗

A Plastidial Glycolytic-Gluconeogenic Switch of Mitochondrial Origin Enables Diatom Adaptations to High Latitudes

Organic carbon fixed in chloroplasts through the Calvin Cycle can be diverted towards different metabolic fates, including cytoplasmic and mitochondrial respiration; gluconeogenesis; and synthesis of diverse plastid metabolites via the pyruvate hub. In plants, pyruvate is principally produced via cytoplasmic glycolysis, although a plastid-targeted lower glycolytic pathway is known in non-photosynthetic tissue. Here, we characterize a lower plastid glycolytic-gluconeogenesis pathway in diatoms, ecologically important marine algae distantly related to plants. We show that two reversible enzymes required to complete diatom plastid glycolysis-gluconeogenesis, Enolase and PGAM (bis- phospho-glycerate mutase), originated through duplications of mitochondria-targeted respiratory isoforms. Through CRISPR-Cas9 mutagenesis, integrative omic analyses, and measured kinetics of expressed enzymes in the diatom Phaeodactylum tricornutum, we present evidence that this pathway diverts plastid glyceraldehyde-3-phosphate into the pyruvate hub, and may also function in the gluconeogenic direction. Considering experimental data, we show that this pathway has different roles dependent in particular on day length and environmental temperature, and show that it is expressed at elevated levels in high latitude oceans where diatoms are abundant. Our data provide evolutionary, meta-genomic and functional insights into a poorly understood yet evolutionarily recurrent plastid metabolic pathway.

plant biology↗

The evo-MOTiF pipeline and database for studying protein motif evolution in a structural context

Short linear motifs (SLiMs) in proteins are short functionally independent sequence stretches with a defined function and required for proteins to interact with their environment. Their functional importance makes it interesting to analyse SLiM features further, such as their structural or evolutionary properties, to understand better how SLiMs evolve to shape protein functions. We developed an automated pipeline to analyse features of SLiMs, called evo-MOTiF. This pipeline takes as input a single protein sequence and its associated SLiM(s) and returns a set of scores associated with SLiM features, including their disorder, as well as their overall, positional and amino acid property conservation. To store and easily mine data from the evo-MOTiF pipeline, we developed the evo-MOTiF database, which currently holds [~]9500 motifs, combining data from ELM, PhosphoSitePlus, as well as from cross-linking mass-spectrometry (XL-MS) experiments. The evo-MOTiF database distinguishes itself further by allowing effortless filtering for SLiMs with specific properties, such as disorder, or conservation in evolution and by providing evolutionary, as well as structural information for SLiMs. Preliminary analysis of SLiM features reveals weak negative correlation between disorder and overall, positional, as well as amino acid property conservation, which is in support of previous observations on smaller datasets. The evo-MOTiF pipeline and database are freely available at https://gitlab.com/habermann_lab/slims and http://etnadb.ibdm.univ-mrs.fr/index.php, respectively.

bioinformatics↗