SidF, a dual substrate N5-acetyl-N5-hydroxy-L-ornithine transacetylase involved in siderophore biosynthesis.

Siderophore-mediated iron acquisition is essential for the virulence of , a fungus causing life-threatening aspergillosis. Drugs targeting the siderophore biosynthetic pathway could help improve disease management. The transacetylases SidF and SidL generate intermediates for different siderophores in .

Unveiling the immunomodulatory dance: endothelial cells' function and their role in non-small cell lung cancer.

The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment play a critical role in the progression of non-small cell lung cancer (NSCLC). In general, endothelial cells exhibit diverse immunomodulatory properties, influencing immune cell recruitment, antigen presentation, and regulation of immune checkpoint expression. Understanding the multifaceted roles of TECs as well as assigning specific functional hallmarks to various TEC phenotypes offer new avenues for targeted development of therapeutic interventions, particularly in the context of advanced immunotherapy and anti-angiogenic treatments.

Cellular damage triggers mechano-chemical control of cell wall dynamics and patterned cell divisions in plant healing.

Reactivation of cell division is crucial for the regeneration of damaged tissues, which is a fundamental process across all multicellular organisms. However, the mechanisms underlying the activation of cell division in plants during regeneration remain poorly understood. Here, we show that single-cell endodermal ablation generates a transient change in the local mechanical pressure on neighboring pericycle cells to activate patterned cell division that is crucial for tissue regeneration in Arabidopsis roots.

Proteome-wide non-cleavable crosslink identification with MS Annika 3.0 reveals the structure of the C. elegans Box C/D complex.

The field of crosslinking mass spectrometry has seen substantial advancements over the past decades, enabling the structural analysis of proteins and protein complexes and serving as a powerful tool in protein-protein interaction studies. However, data analysis of large non-cleavable crosslink studies is still a mostly unsolved problem due to its n-squared complexity. We here introduce an algorithm for the identification of non-cleavable crosslinks implemented in our crosslinking search engine MS Annika that is based on sparse matrix multiplication and allows for proteome-wide searches on commodity hardware.

m6A sites in the coding region trigger translation-dependent mRNA decay.

N-Methyladenosine (m6A) is the predominant internal RNA modification in eukaryotic messenger RNAs (mRNAs) and plays a crucial role in mRNA stability. Here, using human cells, we reveal that m6A sites in the coding sequence (CDS) trigger CDS-m6A decay (CMD), a pathway that is distinct from previously reported m6A-dependent degradation mechanisms. Importantly, CDS m6A sites act considerably faster and more efficiently than those in the 3' untranslated region, which to date have been considered the main effectors.

Shift in diet composition of a riparian predator along a stream pollution gradient.

Terrestrial insectivores in riparian areas, such as spiders, can depend on emergent aquatic insects as high-quality prey. However, chemical pollution entering streams from agricultural and urban sources can alter the dynamics and composition of aquatic insect emergence, which may also affect the riparian food web. Few studies have examined the effects of stressor-induced alterations in aquatic insect emergence on spiders, especially in terms of chemical pollution and diet composition.

An expanded view of cell competition.

Cell competition arises in heterogeneous tissues when neighbouring cells sense their relative fitness and undergo selection. It has been a challenge to define contexts in which cell competition is a physiologically relevant phenomenon and to understand the cellular features that underlie fitness and fitness sensing. Drawing on examples across a range of contexts and length scales, we illuminate molecular and cellular features that could underlie fitness in diverse tissue types and processes to promote and reinforce long-term maintenance of tissue function.

UCBShift 2.0: Bridging the Gap from Backbone to Side Chain Protein Chemical Shift Prediction for Protein Structures.

Chemical shifts are a readily obtainable NMR observable that can be measured with high accuracy, and because they are sensitive to conformational averages and the local molecular environment, they yield detailed information about protein structure in solution. To predict chemical shifts of protein structures, we introduced the UCBShift method that uniquely fuses a transfer prediction module, which employs sequence and structure alignments to select reference chemical shifts from an experimental database, with a machine learning model that uses carefully curated and physics-inspired features derived from X-ray crystal structures to predict backbone chemical shifts for proteins. In this work, we extend the UCBShift 1.

Disentangling the Complexity in Protein Complexes Using Complementary Isotope-Labeling and Multiple-Receiver NMR Spectroscopy.

Intrinsically disordered proteins are abundant in eukaryotic systems, but they remain largely elusive pharmacological targets. NMR spectroscopy proved to be a suitable method to study these proteins and their interaction with one another or with drug candidates. Although NMR can give atomistic information about these interplays, molecular complexity due to severe spectral overlap, limited sample stability, and quantity remain an issue and hamper widespread applications.

New Bacillus paralicheniformis strain with high proteolytic and keratinolytic activity.

Bacillus paralicheniformis T7, which exhibits high proteolytic and keratinolytic activities, was isolated from soil in Kazakhstan. Its secreted proteases were thermostable and alkaline, demonstrating maximum activity at 70 °C and pH 9.0.

Lamin chromatin binding is modulated by interactions of different LAP2α domains with lamins and chromatin.

Lamins A and C are components of the lamina at the nuclear periphery and associate with heterochromatin. A distinct, relatively mobile pool of lamin A/C in the nuclear interior associates with euchromatic regions and with lamin-associated polypeptide 2α (LAP2α). Here we show that phosphorylation-dependent impairment of lamin assembly had no effect on its chromatin association, while LAP2α depletion was sufficient to increase chromatin association of lamins.

Patterns of early post-disturbance reorganization in Central European forests.

Disturbances catalyse change in forest ecosystems, and a climate-driven increase in disturbance activity could accelerate forest reorganization. Here, we studied post-disturbance forests after the biggest pulse of tree mortality in Central Europe in at least 170 years, caused by drought and bark beetle (Scolytinae) outbreaks in 2018-2020. Our objectives were to characterize the early state of tree regeneration after mortality, quantify patterns of reorganization relative to undisturbed reference conditions and assess how management and patch size affect forest reorganization after disturbance.

The future of integrated structural biology.

Instruct-ERIC, "the European Research Infrastructure Consortium for Structural biology research," is a pan-European distributed research infrastructure making high-end technologies and methods in structural biology available to users. Here, we describe the current state-of-the-art of integrated structural biology and discuss potential future scientific developments as an impulse for the scientific community, many of which are located in Europe and are associated with Instruct. We reflect on where to focus scientific and technological initiatives within the distributed Instruct research infrastructure.

Synthesis of a C/H Labeled Building Block to Probe the Phosphotyrosine Interactome Using Biomolecular NMR Spectroscopy.

Phosphotyrosine (pTyr) recognition coordinates the assembly of protein complexes, thus controlling key events of cell cycle, cell development and programmed cell death. Although many aspects of membrane receptor function and intracellular signal transduction have been deciphered in the last decades, the details of how phosphorylation alters protein-protein interaction and creates regulating switches of protein activity and localization often remains unclear. We developed a synthetic route to a protected phophotyrosine building block with isolated C-H spins in the aromatic ring.

The C-terminus of CFAP410 forms a tetrameric helical bundle that is essential for its localization to the basal body.

Cilia are antenna-like organelles protruding from the surface of many cell types in the human body. Defects in ciliary structure or function often lead to diseases that are collectively called ciliopathies. Cilia and flagella-associated protein 410 (CFAP410) localizes at the basal body of cilia/flagella and plays essential roles in ciliogenesis, neuronal development and DNA damage repair.

Mechanisms determining the multi-diversity of carrion visiting species along a gradient of carrion body mass.

Resource availability and habitat heterogeneity are essential drivers of biodiversity, but their individual roles often remain unclear since both factors are often correlated. Here, we tested the more-individuals hypothesis (MIH) and the habitat-heterogeneity hypothesis (HHH) for bacteria, fungi, dipterans, coleopterans, birds, and mammals on 100 experimentally exposed carcasses ranging by three orders of magnitude in body mass. At the level of each carcass we found marginal or significant support for the MIH for bacteria, fungi, and beetles in spring and significant support for fungi, dipterans, and mammals in summer.

LAP2alpha facilitates myogenic gene expression by preventing nucleoplasmic lamin A/C from spreading to active chromatin regions.

A-type lamins form a filamentous meshwork beneath the nuclear membrane that anchors large heterochromatic genomic regions at the nuclear periphery. A-type lamins also exist as a dynamic, non-filamentous pool in the nuclear interior, where they interact with lamin-associated polypeptide 2 alpha (LAP2α). Both proteins associate with largely overlapping euchromatic genomic regions in the nucleoplasm, but the functional significance of this interaction is poorly understood.

Effect of hypoxia on GLP-1 secretion - an in vitro study using enteroendocrine STC-1 -cells as a model.

Glucagon-like peptide (GLP)-1 is a hormone released by enteroendocrine L-cells after food ingestion. L-cells express various receptors for nutrient sensing including G protein-coupled receptors (GPRs). Intestinal epithelial cells near the lumen have a lower O tension than at the base of the crypts, which leads to hypoxia in L-cells.

Probing Protein-Ligand Methyl-π Interaction Geometries through Chemical Shift Measurements of Selectively Labeled Methyl Groups.

Fragment-based drug design is heavily dependent on the optimization of initial low-affinity binders. Herein we introduce an approach that uses selective labeling of methyl groups in leucine and isoleucine side chains to directly probe methyl-π contacts, one of the most prominent forms of interaction between proteins and small molecules. Using simple NMR chemical shift perturbation experiments with selected BRD4-BD1 binders, we find good agreement with a commonly used model of the ring-current effect as well as the overall interaction geometries extracted from the Protein Data Bank.

Oligoclonal CD4CXCR5 T cells with a cytotoxic phenotype appear in tonsils and blood.

In clinical situations, peripheral blood accessible CD3CD4CXCR5 T-follicular helper (T) cells may have to serve as a surrogate indicator for dysregulated germinal center responses in tissues. To determine the heterogeneity of T cells in peripheral blood versus tonsils, CD3CD4CD45RACXCR5 cells of both origins were sorted. Transcriptomes, TCR repertoires and cell-surface protein expression were analysed by single-cell RNA sequencing, flow cytometry and immunohistochemistry.

Museomics help resolving the phylogeny of snowfinches (Aves, Passeridae, Montifringilla and allies).

Historical specimens from museum collections provide a valuable source of material also from remote areas or regions of conflict that are not easily accessible to scientists today. With this study, we are providing a taxon-complete phylogeny of snowfinches using historical DNA from whole skins of an endemic species from Afghanistan, the Afghan snowfinch, Pyrgilauda theresae. To resolve the strong conflict between previous phylogenetic hypotheses, we generated novel mitogenome sequences for selected taxa and genome-wide SNP data using ddRAD sequencing for all extant snowfinch species endemic to the Qinghai-Tibet Plateau (QTP) and for an extended intraspecific sampling of the sole Central and Western Palearctic snowfinch species (Montifringilla nivalis).