WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging.

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY).

Low-molecular weight sulfated marine polysaccharides: Promising molecules to prevent neurodegeneration in mucopolysaccharidosis IIIA?

Mucopolysaccharidosis IIIA is a hereditary disease caused by mutations in the sulfamidase enzyme that participates in catabolism of heparan sulfate (HS), leading to HS fragment accumulation and multisystemic failure. No cure exists and death occurs around the second decade of life. Two low molecular weight highly sulfated compounds derived from marine diabolican and infernan exopolysaccharides (A5_3 and A5_4, respectively) with heparanase inhibiting properties were tested in a MPSIIIA cell line model, resulting in limited degradation of intracellular HS.

HMGB1 cleavage by complement C1s and its potent anti-inflammatory product.

Complement C1s association with the pathogenesis of several diseases cannot be simply explained only by considering its main role in activating the classical complement pathway. This suggests that non-canonical functions are to be deciphered for this protease. Here the focus is on C1s cleavage of HMGB1 as an auxiliary target.

Lipoprotein interactions with water-soluble NIR-II emitting aza-BODIPYs boost the fluorescence signal and favor selective tumor targeting.

Following intravenous administration, the interaction of fluorescent exogenous molecules with circulating endogenous transporters can influence their photophysical properties as well as their fate and distribution, and possibly their recognition by different cell types. This type of interaction can be used to optimize the drug delivery but also the imaging properties of a compound of interest. In this study, we investigated the behavior of SWIR-WAZABY-01 fluorophore, a water-soluble aza-BODIPY dye emitting in the NIR-II region, both and .

Extracellular endosulfatase Sulf-2 harbors a chondroitin/dermatan sulfate chain that modulates its enzyme activity.

Sulfs represent a class of unconventional sulfatases which provide an original post-synthetic regulatory mechanism for heparan sulfate polysaccharides and are involved in multiple physiopathological processes, including cancer. However, Sulfs remain poorly characterized enzymes, with major discrepancies regarding their in vivo functions. Here we show that human Sulf-2 (HSulf-2) harbors a chondroitin/dermatan sulfate glycosaminoglycan (GAG) chain, attached to the enzyme substrate-binding domain.

FGF-2 promotes angiogenesis through a SRSF1/SRSF3/SRPK1-dependent axis that controls VEGFR1 splicing in endothelial cells.

Background: Angiogenesis is the process by which new blood vessels arise from pre-existing ones. Fibroblast growth factor-2 (FGF-2), a leading member of the FGF family of heparin-binding growth factors, contributes to normal as well as pathological angiogenesis. Pre-mRNA alternative splicing plays a key role in the regulation of cellular and tissular homeostasis and is highly controlled by splicing factors, including SRSFs.

Two Different Missense Mutations, Associated to Periodontal Ehlers-Danlos Syndrome, Lead to Identical Molecular Outcomes.

Ehlers-Danlos syndromes (EDS) are clinically and genetically heterogeneous disorders characterized by soft connective tissue alteration like joint hypermobility and skin hyper-extensibility. We previously identified heterozygous missense mutations in the and genes, coding for the complement C1 proteases, in patients affected by periodontal EDS, a specific EDS subtype hallmarked by early severe periodontitis leading to premature loss of teeth and connective tissue alterations. Up to now, there is no clear molecular link relating the nominal role of the C1r and C1s proteases, which is to activate the classical complement pathway, to these heterogeneous symptoms of periodontal EDS syndrome.

Corrigendum: Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome.

[This corrects the article DOI: 10.3389/fimmu.2019.

Mutations Trigger Constitutive Complement 1 Activation in Periodontal Ehlers-Danlos Syndrome.

Heterozygous missense or in-frame insertion/deletion mutations in complement 1 subunits C1r and C1s cause periodontal Ehlers-Danlos Syndrome (pEDS), a specific EDS subtype characterized by early severe periodontal destruction and connective tissue abnormalities like easy bruising, pretibial haemosiderotic plaques, and joint hypermobility. We report extensive functional studies of 16 variants associated with pEDS by overexpression studies in HEK293T cells followed by western blot, size exclusion chromatography and surface plasmon resonance analyses. Patient-derived skin fibroblasts were analyzed by western blot and Enzyme-linked Immunosorbent Assay (ELISA).

Interaction of C1q With Pentraxin 3 and IgM Revisited: Mutational Studies With Recombinant C1q Variants.

Pentraxins and complement defense collagens are soluble recognition proteins that sense pathogens and altered-self elements, and trigger immune responses including complement activation. PTX3 has been shown to interact with the globular recognition domains (gC1q) of the C1q protein of the classical complement pathway, thereby modulating complement activity. The C1q-PTX3 interaction has been characterized previously by site-specific mutagenesis using individual gC1q domains of each of the three C1q chains.

Automated Buildup of Biomimetic Films in Cell Culture Microplates for High-Throughput Screening of Cellular Behaviors.

An automatic method is established for layer-by-layer (LbL) assembly of biomimetic coatings in cell culture microplates using a commercial liquid-handling robot. Highly homogeneous thin films are formed at the bottom of each microwell. The LbL film-coated microplates are compatible with common cellular assays, using microplate readers and automated microscopes.

Role of Phosphorylation in Moesin Interactions with PIP-Containing Biomimetic Membranes.

Moesin, a protein of the ezrin, radixin, and moesin family, which links the plasma membrane to the cytoskeleton, is involved in multiple physiological and pathological processes, including viral budding and infection. Its interaction with the plasma membrane occurs via a key phosphoinositide, the phosphatidyl(4,5)inositol-bisphosphate (PIP), and phosphorylation of residue T558, which has been shown to contribute, in cellulo, to a conformationally open protein. We study the impact of a double phosphomimetic mutation of moesin (T235D, T558D), which mimics the phosphorylation state of the protein, on protein/PIP/microtubule interactions.

Biomaterial-enabled delivery of SDF-1α at the ventral side of breast cancer cells reveals a crosstalk between cell receptors to promote the invasive phenotype.

The SDF-1α chemokine (CXCL12) is a potent bioactive chemoattractant known to be involved in hematopoietic stem cell homing and cancer progression. The associated SDF-1α/CXCR4 receptor signaling is a hallmark of aggressive tumors, which can metastasize to distant sites such as lymph nodes, lung and bone. Here, we engineered a biomimetic tumoral niche made of a thin and soft polyelectrolyte film that can retain SDF-1α to present it, in a spatially-controlled manner, at the ventral side of the breast cancer cells.

Binding of the chemokine CXCL12α to its natural extracellular matrix ligand heparan sulfate enables myoblast adhesion and facilitates cell motility.

The chemokine CXCL12α is a potent chemoattractant that guides the migration of muscle precursor cells (myoblasts) during myogenesis and muscle regeneration. To study how the molecular presentation of chemokines influences myoblast adhesion and motility, we designed multifunctional biomimetic surfaces as a tuneable signalling platform that enabled the response of myoblasts to selected extracellular cues to be studied in a well-defined environment. Using this platform, we demonstrate that CXCL12α, when presented by its natural extracellular matrix ligand heparan sulfate (HS), enables the adhesion and spreading of myoblasts and facilitates their active migration.

The effect of delivering the chemokine SDF-1α in a matrix-bound manner on myogenesis.

Several chemokines are important in muscle myogenesis and in the recruitment of muscle precursors during muscle regeneration. Among these, the SDF-1α chemokine (CXCL12) is a potent chemoattractant known to be involved in muscle repair. SDF-1α was loaded in polyelectrolyte multilayer films made of poly(L-lysine) and hyaluronan to be delivered locally to myoblast cells in a matrix-bound manner.

Binding of moesin and ezrin to membranes containing phosphatidylinositol (4,5) bisphosphate: a comparative study of the affinity constants and conformational changes.

The plasma membrane-cytoskeleton interface is a dynamic structure participating in a variety of cellular events. Moesin and ezrin, proteins from the ezrin/radixin/moesin (ERM) family, provide a direct linkage between the cytoskeleton and the membrane via their interaction with phosphatidylinositol 4,5-bisphosphate (PIP(2)). PIP(2) binding is considered as a prerequisite step in ERM activation.