Protein dynamics at invadopodia control invasion-migration transitions in melanoma cells.

Cell invasion is a highly complex process that requires the coordination of cell migration and degradation of the extracellular matrix. In melanoma cells, as in many highly invasive cancer cell types these processes are driven by the regulated formation of adhesives structures such as focal adhesions and invasive structures like invadopodia. Structurally, focal adhesion and invadopodia are quite distinct, yet they share many protein constituents.

Inhibiting FAK-Paxillin Interaction Reduces Migration and Invadopodia-Mediated Matrix Degradation in Metastatic Melanoma Cells.

The nonreceptor tyrosine kinase FAK is a promising target for solid tumor treatment because it promotes invasion, tumor progression, and drug resistance when overexpressed. Investigating the role of FAK in human melanoma cells, we found that both in situ and metastatic melanoma cells strongly express FAK, where it controls tumor cells' invasiveness by regulating focal adhesion-mediated cell motility. Inhibiting FAK in human metastatic melanoma cells with either siRNA or a small inhibitor targeting the kinase domain impaired migration but led to increased invadopodia formation and extracellular matrix degradation.

The Cofactors of Nitrogenases.

In biological nitrogen fixation, the enzyme nitrogenase mediates the reductive cleavage of the stable triple bond of gaseous N2at ambient conditions, driven by the hydrolysis of ATP, to yield bioavailable ammonium (NH4+). At the core of nitrogenase is a complex, ironsulfur based cofactor that in most variants of the enzyme contains an additional, apical heterometal (Mo or V), an organic homocitrate ligand coordinated to this heterometal, and a unique, interstitial carbide. Recent years have witnessed fundamental advances in our understanding of the atomic and electronic structure of the nitrogenase cofactor.

Concentration-Dependent Seeding as a Strategy for Fabrication of Densely Packed Surface-Mounted Metal-Organic Frameworks (SURMOF) Layers.

The layer-by-layer (LbL) method is a well-established method for the growth of surface-attached metal-organic frameworks (SURMOFs). Various experimental parameters, such as surface functionalization or temperature, have been identified as essential in the past. In this study, inspired by these recent insights regarding the LbL SURMOF growth mechanism, the impact of reactant solutions concentration on LbL growth of the Cu (F bdc) (dabco) SURMOF (F bdc =tetrafluorobenzene-1,4-dicarboxylate and dabco=1,4-diazabicyclo-[2.

A bound reaction intermediate sheds light on the mechanism of nitrogenase.

Reduction of N by nitrogenases occurs at an organometallic iron cofactor that commonly also contains either molybdenum or vanadium. The well-characterized resting state of the cofactor does not bind substrate, so its mode of action remains enigmatic. Carbon monoxide was recently found to replace a bridging sulfide, but the mechanistic relevance was unclear.

A Metabolomic Approach (H HRMAS NMR Spectroscopy) Supported by Histology to Study Early Post-transplantation Responses in Islet-transplanted Livers.

Intrahepatic transplantation of islets requires a lot of islets because more than 50% of the graft is lost during the 24 hours following transplantation. We analyzed, in a rat model, early post-transplantation inflammation using systemic inflammatory markers, or directly in islet-transplanted livers by immunohistochemistry. H HRMAS NMR was employed to investigate metabolic responses associated with the transplantation.

Expression/activation of α5β1 integrin is linked to the β-catenin signaling pathway to drive migration in glioma cells.

The Wnt/beta catenin pathway has been highlighted as an important player of brain tumors aggressiveness and resistance to therapies. Increasing knowledges of the regulation of beta-catenin transactivation point out its hub position in different pathophysiological outcomes in glioma such as survival and migration. Crosstalks between integrins and beta-catenin pathways have been suggested in several tumor tissues.

The Child-care Food and Activity Practices Questionnaire (CFAPQ): development and first validation steps.

Objective: To develop and validate a questionnaire to measure food-related and activity-related practices of child-care staff, based on existing, validated parenting practices questionnaires.

Design: A selection of items from the Comprehensive Feeding Practices Questionnaire (CFPQ) and the Preschooler Physical Activity Parenting Practices (PPAPP) questionnaire was made to include items most suitable for the child-care setting. The converted questionnaire was pre-tested among child-care staff during cognitive interviews and pilot-tested among a larger sample of child-care staff.

CD47 activation-induced UHRF1 over-expression is associated with silencing of tumor suppressor gene p16INK4A in glioblastoma cells.

CD47, an integrin-associated protein is over-expressed in several tumors including glioblastomas. Activation of CD47 induces proliferation of human astrocytoma cells but not normal astrocytes via an Akt-dependent way. However, the pathways mediating this process are still unknown.

Pro-inflammatory and pro-oxidant status of pancreatic islet in vitro is controlled by TLR-4 and HO-1 pathways.

Since their isolation until implantation, pancreatic islets suffer a major stress leading to the activation of inflammatory reactions. The maintenance of controlled inflammation is essential to preserve survival and function of the graft. Identification and targeting of pathway(s) implicated in post-transplant detrimental inflammatory events, is mandatory to improve islet transplantation success.

FAK competes for Src to promote migration against invasion in melanoma cells.

Melanoma is one of the most deadly cancers because of its high propensity to metastasis, a process that requires migration and invasion of tumor cells driven by the regulated formation of adhesives structures like focal adhesions (FAs) and invasive structures like invadopodia. FAK, the major kinase of FAs, has been implicated in many cellular processes, including migration and invasion. In this study, we investigated the role of FAK in the regulation of invasion.

TiO2 photocatalysis damages lipids and proteins in Escherichia coli.

This study investigates the mechanisms of UV-A (315 to 400 nm) photocatalysis with titanium dioxide (TiO2) applied to the degradation of Escherichia coli and their effects on two key cellular components: lipids and proteins. The impact of TiO2 photocatalysis on E. coli survival was monitored by counting on agar plate and by assessing lipid peroxidation and performing proteomic analysis.

Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16 INK4A re-expression related to UHRF1 and DNMT1 down-regulation.

Several reports have described the potential effects of natural compounds as anti-cancer agents in vitro as well as in vivo. The aim of this study was to evaluate the anti-cancer effect of Limoniastrum guyonianum aqueous gall extract (G extract) and luteolin in the human cervical cancer HeLa cell line, and, if so, to clarify the underlying mechanism. Our results show that G extract and luteolin inhibited cell proliferation and induced G2/M cell cycle arrest in a concentration and time-dependent manner.

On the use of capillary cytometry for assessing the bactericidal effect of TiO2. Identification and involvement of reactive oxygen species.

The photocatalytic antimicrobial properties of TiO2 were studied on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa bacterial strains taken as model strains for pathogenic species mainly implied in nosocomial infections. Capillary cytometry, coupled to a double-staining method for visualizing membrane integrity as a cell viability indicator, was highlighted as a rapid, easy-to-use, and automated numeration technique for quantitative and reproducible determination of cellular viability and thus, was able to give an accurate evaluation of the bactericidal effect of UV-A photocatalysis. Cytometry also enabled the study of TiO2-bacteria interactions and aggregation in the dark as well as TiO2 cytotoxicity.

Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation.

Glioblastoma represent the most frequent primary tumors of the central nervous system and remain among the most aggressive human cancers as available therapeutic approaches still fail to contain their invasiveness. Many studies have reported elevated expression of the Focal Adhesion Kinase (FAK) protein in glioblastoma, associated with an increase in the rates of both migration and invasion. This designates FAK as a promising target to limit invasiveness in glioblastoma.

Instant blood-mediated inflammatory reaction during islet transplantation: the role of Toll-like receptors signaling pathways.

The instant blood-mediated inflammatory reaction (IBMIR) leads to massive destruction of transplanted islets. Islet isolation and time of culture may elicit the release of potent activators of Toll-like receptors (TLRs) signaling pathways during IBMIR. This work sought to evaluate the role of TLR signaling pathways to mediate inflammatory reactions.

Anti-neoplastic agent thymoquinone induces degradation of α and β tubulin proteins in human cancer cells without affecting their level in normal human fibroblasts.

The microtubule-targeting agents derived from natural products, such as vinca-alkaloids and taxanes are an important family of efficient anti-cancer drugs with therapeutic benefits in both haematological and solid tumors. These drugs interfere with the assembly of microtubules of α/β tubulin heterodimers without altering their expression level. The aim of the present study was to investigate the effect of thymoquinone (TQ), a natural product present in black cumin seed oil known to exhibit putative anti-cancer activities, on α/β tubulin expression in human astrocytoma cells (cell line U87, solid tumor model) and in Jurkat cells (T lymphoblastic leukaemia cells).

Constitutive overexpression of muscarinic receptors leads to vagal hyperreactivity.

Background: Alterations in muscarinic receptor expression and acetylcholinesterase (AchE) activity have been observed in tissues from Sudden Infant Death Syndrome (SIDS). Vagal overactivity has been proposed as a possible cause of SIDS as well as of vasovagal syncopes. The aim of the present study was to seek whether muscarinic receptor overexpression may be the underlying mechanism of vagal hyperreactivity.

Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an Akt-dependent pathway.

CD47 is a membrane receptor that plays pivotal roles in many pathophysiological processes, including infection, inflammation, cell spreading, proliferation, and apoptosis. We show that activation of CD47 increases proliferation of human U87 and U373 astrocytoma cells but not normal astrocytes. CD47 function-blocking antibodies inhibit proliferation of untreated U87 and U373 cells but not normal astrocytes, suggesting that CD47 may be constitutively activated in astrocytoma.

Advanced glycation end products (AGEs) activate mast cells.

Background And Purpose: Advanced glycation endproducts (AGEs) represent one of the many types of chemical modifications that occur with age in long-lived proteins. AGEs also accumulate in pathologies such as diabetes, cardiovascular diseases, neurodegeneration and cancer. Mast cells are major effectors of acute inflammatory responses that also contribute to the progression of chronic diseases.

Emergency department tachypnea predicts transfer to a higher level of care in the first 24 hours after ED admission.

Objectives: The authors hypothesized that vital sign abnormalities detected in the emergency department (ED) can be used to forecast clinical deterioration occurring within 24 hours of hospital admission.

Methods: This was a retrospective case-control study performed after implementation of a hospitalwide rapid response team (RRT) system. Inclusion criteria for study patients consisted of age > or = 18 years, admission to the general floor though the ED, and RRT activation and subsequent transfer to a higher level of care in the first 24 hours.

Cardiac muscarinic receptor overexpression in sudden infant death syndrome.

Background: Sudden infant death syndrome (SIDS) remains the leading cause of death among infants less than 1 year of age. Disturbed expression of some neurotransmitters and their receptors has been shown in the central nervous system of SIDS victims but no biological abnormality of the peripheral vago-cardiac system has been demonstrated to date. The present study aimed to seek vago-cardiac abnormalities in SIDS victims.

Complement receptor 3 (CD11b/CD18) is implicated in the elimination of β-amyloid peptides.

Microglia are the professional phagocytes of the brain and express phagocytic receptors such as complement receptor 3 (CR3 or CD11b/CD18). Using mimics of the amyloid deposit made of heat-killed yeasts coated with either Aβ 1-40 or Aβ 1-42, we were able to study how microglia interacted with and ingested these particles in vitro. We have shown previously that the low density lipoprotein receptor-related protein (LRP) is largely implied in the phagocytosis of Aβ 1-42-opsonized heat-killed yeasts and partly in that of Aβ 1-40-opsonized heat-killed yeasts.

Activation of CD47 receptors causes histamine secretion from mast cells.

Mast cells play pivotal roles in allergic and inflammatory processes via distinct activation pathways. Mucosal and serosal mast cells are activated by the IgE/FcepsilonRI pathway, while only serosal mast cells are activated by basic secretagogues. We show that CD47 receptors are expressed on rat peritoneal mast cells.

Drugs and their molecular targets: an updated overview.

About 330 targets bind approved drugs, 270 encoded by the human genome and 60 belonging to pathogenic organisms. A large number of druggable targets have been recently proposed from preclinical and first clinical data, but a huge reservoir of putative drug targets, possibly several thousands, remains to be explored. This overview considers the different types of ligands and their selectivity in the main superfamilies of drug targets, enzymes, membrane transporters and ion channels, and the various classes of membrane and nuclear receptors with their signalling pathway.