Identification of Cellular Protein Targets of a Half-Sandwich Iridium(III) Complex Reveals Its Dual Mechanism of Action via Both Electrophilic and Oxidative Stresses.

Identification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C∧N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high-affinity targets.

Morphology and distribution of sensilla on head appendages in the water beetle Hygrobia hermanni (Coleoptera: Adephaga: Hygrobiidae).

Sensilla on head appendages were studied in detail for the first time in a member of the relict family Hygrobiidae (squeak beetles), closely related to Dytiscidae (diving beetles). Adult and third instar larval stage specimens of Hygrobia hermanni (Fabricius, 1775) were examined using scanning electron microscopy, focusing on antennae, palps and larval mandibles. In total, 37 sensilla subtypes are described, including 22 observed in the adult (basiconica: 3; Böhm's bristles: 2; circumvallate sensilla: 2; coeloconica: 10; ovoid placodea: 3; digitiform placodea: 2) and 16 in the larva (basiconica: 4; campaniformia: 1; chaetica: 4; coeloconica: 5; trichodea: 1; unnamed: 1).

A human septin octamer complex sensitive to membrane curvature drives membrane deformation with a specific mesh-like organization.

Septins are cytoskeletal proteins interacting with the inner plasma membrane and other cytoskeletal partners. Being key in membrane remodeling processes, they often localize at specific micrometric curvatures. To analyze the behavior of human septins at the membrane and decouple their role from other partners, we used a combination of bottom-up in vitro methods.

Pickering emulsions stabilized with biodegradable nanoparticles for the co-encapsulation of two active pharmaceutical ingredients.

Innovative Pickering emulsions co-encapsulating two active pharmaceutical ingredients (API) were formulated for a topical use. An immunosuppressive agent, either cyclosporine A (CysA) or tacrolimus (TAC), was encapsulated at high drug loading in biodegradable and biocompatible poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). These NP stabilized the oil droplets (Miglyol) containing an anti-inflammatory drug, calcitriol (CAL).

Nanoscopic distribution of VAChT and VGLUT3 in striatal cholinergic varicosities suggests colocalization and segregation of the two transporters in synaptic vesicles.

Striatal cholinergic interneurons (CINs) use acetylcholine (ACh) and glutamate (Glut) to regulate the striatal network since they express vesicular transporters for ACh (VAChT) and Glut (VGLUT3). However, whether ACh and Glut are released simultaneously and/or independently from cholinergic varicosities is an open question. The answer to that question requires the multichannel detection of vesicular transporters at the level of single synaptic vesicle (SV).

Bottom-Up In Vitro Methods to Assay the Ultrastructural Organization, Membrane Reshaping, and Curvature Sensitivity Behavior of Septins.

Membrane remodeling occurs constantly at the plasma membrane and within cellular organelles. To fully dissect the role of the environment (ionic conditions, protein and lipid compositions, membrane curvature) and the different partners associated with specific membrane reshaping processes, we undertake in vitro bottom-up approaches. In recent years, there has been keen interest in revealing the role of septin proteins associated with major diseases.

Conjugation of Oligo-His Peptides to Magnetic γ-FeO@SiO Core-Shell Nanoparticles Promotes Their Access to the Cytosol.

The endosomal entrapment of functional nanoparticles is a severe limitation to their use for biomedical applications. In the case of magnetic nanoparticles (MNPs), this entrapment leads to poor heating efficiency for magnetic hyperthermia and suppresses the possibility to manipulate them in the cytosol. Current strategies to limit their entrapment include functionalization with cell-penetrating peptides to promote translocation directly across the cell membrane or facilitate endosomal escape.

Cytokine receptor cluster size impacts its endocytosis and signaling.

The interleukin-2 receptor (IL-2R) is a cytokine receptor essential for immunity that transduces proliferative signals regulated by its uptake and degradation. IL-2R is a well-known marker of clathrin-independent endocytosis (CIE), a process devoid of any coat protein, raising the question of how the CIE vesicle is generated. Here, we investigated the impact of IL-2Rγ clustering in its endocytosis.

Tuning morphology of Pickering emulsions stabilised by biodegradable PLGA nanoparticles: How PLGA characteristics influence emulsion properties.

In this study, we proved that the stabilisation of Pickering emulsions by polymer nanoparticles (NPs) heavily depends on polymer characteristics. We prepared NPs with four poly(lactide-co-glycolide) polymers (PLGA), of different molar masses (14,000 and 32,000 g/mol) and end groups (acid or alkylester). NPs were either bare (without stabilising polymer) or covered by polyvinyl alcohol (PVA).

[A tularemia mimicking lymphoma].

Introduction: Adenopathies are a frequent cause of recourse in internal medicine. When histological analysis reveals the presence of granuloma, multiple infectious or non-infectious etiologies are considered. If diagnoses of lymphoma, sarcoidosis or tuberculosis are easily mentioned, tularemia should also be considered in the differential diagnosis.

Interaction of the Anti-Proliferative GPER Inverse Agonist ERα17p with the Breast Cancer Cell Plasma Membrane: From Biophysics to Biology.

The peptide ERα17p, which corresponds to the 295-311 fragment of the hinge/AF2 domains of the human estrogen receptor α (ERα), exerts apoptosis in breast cancer cells through a mechanism involving the G protein-coupled estrogen-dependent receptor GPER. Besides this receptor-mediated mechanism, we have detected a direct interaction (Kd value in the micromolar range) of this peptide with lipid vesicles mimicking the plasma membrane of eukaryotes. The reversible and not reversible pools of interacting peptide may correspond to soluble and aggregated membrane-interacting peptide populations, respectively.

Clathrin plaques and associated actin anchor intermediate filaments in skeletal muscle.

Clathrin plaques are stable features of the plasma membrane observed in several cell types. They are abundant in muscle, where they localize at costameres that link the contractile apparatus to the sarcolemma and connect the sarcolemma to the basal lamina. Here, we show that clathrin plaques and surrounding branched actin filaments form microdomains that anchor a three-dimensional desmin intermediate filament (IF) web.

Author Correction: TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons.

The originally published version of this Article contained an error in the subheading "Microglial GR does not affect DN loss triggered by TLR4 and TLR7," which was incorrectly given as "Microglial GR does affect DN loss triggered by TLR2 and TLR4". This has now been corrected in both the PDF and HTML versions of the Article.

TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons.

Inflammation is a characteristic feature of Parkinson's disease (PD). We examined the role of TLR9 and its regulation by glucocorticoid receptors (GRs) in degeneration of substantia nigra dopamine neurons (DNs). TLR9 agonist, CpG-ODN, induced DN degeneration in mice lacking GR in microglia but not in controls.

Identification of a new mineralized tissue in the notochord of reared Siberian sturgeon (Acipenser baerii).

In a study aiming to improve knowledge on the mineralization of the axial skeleton in reared Siberian sturgeon (Acipenser baerii Brandt, 1869), we discovered a new mineralized tissue within the notochord. To our knowledge, such a structure has never been reported in any vertebrate species with the exception of the pathological mineralization of the notochord remains in degenerative intervertebral disks of mammals. Here, we describe this enigmatic tissue using X-ray microtomography, histological analyses and solid state NMR-spectroscopy.

Vertebral Development and Ossification in the Siberian Sturgeon (Acipenser Baerii), with New Insights on Bone Histology and Ultrastructure of Vertebral Elements and Scutes.

In order to improve our knowledge on the vertebral development, structure and mineralization in Acipenseriformes, we undertook a study in a growth series of reared Siberian sturgeons (Acipenser baerii) using in toto clear and stain specimens, histological and ultrastructural observations, X-ray micro-tomography, and solid state NMR analyses. Scutes were also studied to compare the tissue structure and mineralization of endoskeletal and dermal skeletal elements. This study completes and clarifies previous investigations on vertebral development and architecture in sturgeons, and brings original data on the structure of (i) the perichondral bone that is progressively deposited around the vertebral elements during ontogeny, (ii) the typical cartilage composing these elements, and (iii) the scutes.

Membrane protrusion powers clathrin-independent endocytosis of interleukin-2 receptor.

Endocytosis controls many functions including nutrient uptake, cell division, migration and signal transduction. A clathrin- and caveolin-independent endocytosis pathway is used by important physiological cargos, including interleukin-2 receptors (IL-2R). However, this process lacks morphological and dynamic data.

OCRL-mutated fibroblasts from patients with Dent-2 disease exhibit INPP5B-independent phenotypic variability relatively to Lowe syndrome cells.

OCRL mutations are associated with both Lowe syndrome and Dent-2 disease, two rare X-linked conditions. Lowe syndrome is an oculo-cerebro-renal disorder, whereas Dent-2 patients mainly present renal proximal tubulopathy. Loss of OCRL-1, a phosphoinositide-5-phosphatase, leads in Lowe patients' fibroblasts to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) accumulation, with defects in F-actin network, α-actinin distribution and ciliogenesis, whereas fibroblasts of Dent-2 patients are still uncharacterized.

The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39.

The formation of the autophagic vesicles requires the recruitment of ubiquitin-like Atg8 proteins to the membrane of nascent autophagosomes. Seven Atg8 homologs are present in mammals, split into the LC3 and the GABARAP/GATE-16 families, whose respective functions are unknown. Using Caenorhabditis elegans, we investigated the functions of the GABARAP and the LC3 homologs, LGG-1 and LGG-2, in autophagosome biogenesis.

[Computers to facilitate the quality of blood products orders].

The decision to order component blood products is perhaps the most critical step in patient's transfusion safety. A variety of techniques used to bring about behavioural changes in the transfusion practices of physicians have been met with limited success. Computerized order entry (CPOE) and decision support systems have been demonstrated to improve the quality of orders in terms of legibility and completeness.

Microwaves and tea: new tools to process plant tissue for transmission electron microscopy.

Optimizing sample processing, reducing the duration of the preparation of specimen, and adjusting procedures to adhere to new health and safety regulations, are the current challenges of plant electron microscopists. To address these issues, plant processing protocols for TEM, combining the use of polyphenolic compounds as substitute for uranyl acetate with microwave technology are being developed. In the present work, we optimized microwave-assisted processing of different types of plant tissue for ultrastuctural and immunocytochemical studies.

The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04.

H5N1 influenza viruses transmitted from poultry to humans in Asia cause high mortality and pose a pandemic threat. Viral genes important for cell tropism and replication efficiency must be identified to elucidate and target virulence factors. We applied reverse genetics to generate H5N1 reassortants combining genes of lethal A/Vietnam/1203/04 (VN1203), a fatal human case isolate, and nonlethal A/chicken/Vietnam/C58/04 (CH58) and tested their pathogenicity in ferrets and mice.

[Fatal pulmonary edema in a pernicious malaria attack].

A case is reported of a 40-year-old woman presenting with cerebral malaria complicated by an adult respiratory distress syndrome (ARDS). The patient was admitted to the intensive care unit in a coma, scored 5 on the Glasgow scale. Plasmodium falciparum parasitaemia was, at the time, 50%.