Boolean versus continuous dynamics on simple two-gene modules

We investigate the dynamical behavior of simple modules composed of two genes with two or three regulating connections. Continuous dynamics for mRNA and protein concentrations is compared to a Boolean model for gene activity. Using a generalized method, we study within a single framework different continuous models and different types of regulatory functions, and establish conditions under which the system can display stable oscillations. These conditions concern the time scales, the degree of cooperativity of the regulating interactions, and the signs of the interactions. Not all models that show oscillations under Boolean dynamics can have oscillations under continuous dynamics, and vice versa.Comment: 8 pages, 10 figure

Using Surface Plasmon Resonance to Quantitatively Assess Lipid-Protein Interactions

Surface Plasmon Resonance (SPR) is a quantitative, label-free method for determining molecular interactions in real time. The technology involves fixing a ligand onto a senor chip, measuring a baseline resonance angle, and flowing an analyte in bulk solution over the fixed ligand to measure the subsequent change in resonance angle. The mass of analyte bound to fixed ligand is directly proportional to the resonance angle change and the system is sensitive enough to detect as little as picomolar amounts of analyte in the bulk solution. SPR can be used to determine both the specificity of molecular interactions and the kinetics and affinity of an interaction. This technique has been especially useful in measuring the affinities of lipid-binding proteins to intact liposomes of varying lipid compositions

A rapid assay for tyrosinase activity

A rapid assay for tyrosinase activit

Pure red cell aplasia induced by epoetin zeta

Pure red cell aplasia (PRCA) may develop in patients with chronic kidney disease receiving erythropoiesis-stimulating agents (ESA). We report on a 72-year-old patient who developed hypo-proliferative anaemia unresponsive to ESA following the administration of epoetin zeta subcutaneously for 7 months. On the basis of severe isolated hypoplasia of the erythroid line in the bone marrow and high-titre neutralizing anti-erythropoietin antibodies (Ab), a diagnosis of Ab-mediated PRCA was made. Epoetin zeta was discontinued and the patient was given steroids. This was associated with anaemia recovery. To our knowledge this is the first PRCA case related to epoetin zeta

Emerging cross-disciplinary profiles: The Geomatic Epidemiologist

Abstract Issue Geographic information systems (GIS) and remote sensing technologies are increasingly used in Public Health epidemiology, showing a great potential in anticipating and responding to actual and future challenges for the public health system and in improving health services' excellence. According to the evidences collected within a wide meta-research carried on of relevant literature ("GIS geographic information system" and "GIS geographic information system and training" on Pubmed; "epidemiologist use of GIS and training" and "epidemiologist use of gis" on Google Scholar),GIS and new sensing technologies are mostly used to: map air and water pollution, map diseases prevalence, predict infection diseases and vector-spread diseases in big areas, study health service coverage and preparedness in emergencies, map cities and study urban health, study climate changes for decision making. Description of the Problem Specific skills and training are required to address the use of GIS and new sensing technologies.The specific aim of our study is to identify the professional profile of a new figure, called 'Geomatic Epidemiologist' and to define its professional and educational standards, as well as the relevant training programs. Results Data collection and analysis of INAPP and ESCO databases about existing professional profiles (starting from 2016) has allowed drafting a first qualification schema and profile. The profile has been defined according to the 4C model (elaborated by Univaq) distinguishing between Hard Skills (technical knowledge and skills),Soft Skills (cognitive, individual and social) and interpersonal behaviors. Conclusions Profile will be validated with relevant stakeholders and Public Health professionals in order to deepen the understanding of the main competences required to study health issues with GIS and related technologies; to this extent, a questionnaire has been elaborated to evaluate relevance, frequency and complexity of each component of the profile Key messages Developing cross-disciplinary profiles, (i.e. the Geomatic Epidemiologist) integrating clusters of competences (holistic approach). Public health research challenges and excellence

ANTIMICROBIAL PEPTIDES ARE TARGETS FOR BACTERIAL ADP-RIBOSYLTRANSFERASE ENZYMES

Background: Human α-defensins (HNPs 1-3) are small cationic, amphipatic peptides with microbicidal activities. HNP-1 is the physiological target of ART1, an arginine (Arg) specific eucaryotic ribosyltransferase enzyme1. Mono ADP-ribosylation of Arg14 of HNP-1 modulates its biological activities2. Bacterial exotoxins like Cholera Toxin (CT) by Vibrio cholerae, Heat Labile Enterotoxin (LT1) by Escherichia coli and Exoenzyme S (ExoS) by Pseudomonas aeruginosa are arginine ADP-ribosyltransferase enzymes that alter cell functions by modifying protein targets. Objectives: 1. Evaluate the ADP ribosylation of HNP-1 by CT, LT1 and ExoS. 2. Purify modified peptides and identify the ADP-ribosylated Arg. Methods: ADP-ribosylation of HNP-1 will be evaluated with biotinilated NAD by western blot. Purification of modified peptides will be performed by reverse phase HPLC. Identification of modification will be performed by Maldi-Toff analysis. Results: 1. CT and LT1 are effective in ADP-ribosylating HNP-1 as equal as the well known activity of ART1. On the other hand ExoS does not recognize HNP-1 as substrate. 2. Ongoing experiments are purifications and characterization of modified peptides by reverse-phase HPLC and Maldi-Toff analysis. Conclusions: 1. The different ADP-ribosylating activities displayed by CT, LT1 and ExoS on HNP-1 might be explained with differences in microbial pathogenesis, as the toxins released by V. cholerae and E. coli are involved in the early stages of infections, during the interactions with surface epithelial cells, while ExoS by P. aeruginosa is active during blood dissemination, when the pathogen has already overcome epithelial barrier. References: 1 Balducci et al., 1999, Am J Respir Cell Mol Biol, 21, 337-46 2 Paone et al., 2006, J Biol Chem, 281, 17054-6

Are Extracted Materials Truly Representative of Original Samples? Impact of C18 Extraction on CDOM Optical and Chemical Properties

Some properties of dissolved organic matter (DOM) and chromophoric dissolved organic matter (CDOM) can be easily measured directly on whole waters, while others require sample concentration and removal of natural salts. To increase CDOM content and eliminate salts, solid phase extraction (SPE) is often employed. Biases following extraction and elution are inevitable, thus raising the question of how truly representative the extracted material is of the original. In this context, we investigated the wavelength dependence of extraction efficiency for C18 cartridges with respect to CDOM optical properties using samples obtained from the Middle Atlantic Bight (MAB) and the Equatorial Atlantic Ocean (EAO). Further, we compared the optical changes of C18 extracts and the corresponding whole water following chemical reduction with sodium borohydride (NaBH4). C18 cartridges preferentially extracted long-wavelength absorbing/emitting material for samples impacted by riverine input. Extraction efficiency overall decreased with offshore distance away from riverine input. Spectral slopes of C18-OM samples were also almost always lower than those of their corresponding CDOM samples supporting the preferential extraction of higher molecular weight absorbing material. The wavelength dependence of the optical properties (absorption, fluorescence emission, and quantum yield) of the original water samples and their corresponding extracted material were very similar. C18 extracts and corresponding water samples further exhibited comparable optical changes following NaBH4 reduction, thus suggesting a similarity in nature (structure) of the optically active extracted material, independent of geographical locale. Altogether, these data suggested a strong similarity between C18 extracts and corresponding whole waters, thus indicating that extracts are representative of the CDOM content of original waters

Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T-cells and tumour cells

Extracellular vesicles (EVs) mediate the cross-talk between cancer cells and the cells of the surrounding Tumour Microenvironment (TME). Professional killer cells include Natural Killer (NK) cells and CD8+ Cytotoxic T-lymphocytes (CTLs), which represent some of the most effective immune defense mechanisms against cancer cells. Recent evidence supports the role of EVs released by NK cells and CTLs in killing cancer cells, paving the road to a possible therapeutic role for such EVs. This review article provides the state-of-the-art knowledge on the role of NK- and CTL-derived EVs as anticancer agents, focusing on the different functions of different sub-types of EVs. We also reviewed the current knowledge on the effects of cancer-derived EVs on NK cells and CTLs, identifying areas for future investigation in the emerging new field of EV-mediated immunotherapy of cancer

Spinal motoneurons of the human newborn are highly synchronized during leg movements

Motoneurons of neonatal rodents show synchronous activity that modulates the development of the neuromuscular system. However, the characteristics of the activity of human neonatal motoneurons are largely unknown. Using a noninvasive neural interface, we identified the discharge timings of individual spinal motoneurons in human newborns. We found highly synchronized activities of motoneurons of the tibialis anterior muscle, which were associated with fast leg movements. Although neonates' motor units exhibited discharge rates similar to those of adults, their synchronization was significantly greater than in adults. Moreover, neonatal motor units showed coherent oscillations in the delta band, which is directly translated into force generation. These results suggest that motoneuron synchronization in human neonates might be an important mechanism for controlling fast limb movements, such as those of primitive reflexes. In addition to help revealing mechanisms of development, the proposed neural interface might monitor children at risk of developing motor disorders