Human neutrophils phagocytose and kill Acinetobacter baumanii and A. pittii

Acinetobacter baumannii is a common cause of health care associated infections worldwide. A. pittii is an opportunistic pathogen also frequently isolated from Acinetobacter infections other than those from A. baumannii. Knowledge of Acinetobacter virulence factors and their role in pathogenesis is scarce. Also, there are no detailed published reports on the interactions between A. pittii and human phagocytic cells. Using confocal laser and scanning electron microscopy, immunofluorescence, and live-cell imaging, our study shows that immediately after bacteria-cell contact, neutrophils rapidly and continuously engulf and kill bacteria during at least 4 hours of infection in vitro. After 3 h of infection, neutrophils start to release neutrophil extracellular traps (NETs) against Acinetobacter. DNA in NETs colocalizes well with human histone H3 and with the specific neutrophil elastase. We have observed that human neutrophils use large filopodia as cellular tentacles to sense local environment but also to detect and retain bacteria during phagocytosis. Furthermore, co-cultivation of neutrophils with human differentiated macrophages before infections shows that human neutrophils, but not macrophages, are key immune cells to control Acinetobacter. Although macrophages were largely activated by both bacterial species, they lack the phagocytic activity demonstrated by neutrophils

The census as an information source in public policy-making

This paper provides an assessment of the value of national population censuses as information sources with specific reference toUK census data and its use in policy-making. Mixed methods were adopted to collect quantitative and qualitative data from twosources: (1) a content analysis of policy documents, and (2) interviews with policy-makers in Scotland. The findings highlight thatalthough the general value of the census is recognised, policy-makers are not necessarily closely engaged with the census as a toolfor directing the development and implementation of policy. This is evident, for example in a lack of awareness of proposed changesto the census, and infrequent deployment of available data. The opportunity to change perceptions among policy-makers, and toexpand the application of census data in public policy, is identified. With a novel focus on the deployment of censuses as sources ofevidence for policy-making that includes the views of policy-makers from both within and beyond government, this workcontributes to an established body of global research on international censuses

Epithelial antimicrobial peptides in host defense against infection

One component of host defense at mucosal surfaces seems to be epithelium-derived antimicrobial peptides. Antimicrobial peptides are classified on the basis of their structure and amino acid motifs. Peptides of the defensin, cathelicidin, and histatin classes are found in humans. In the airways, α-defensins and the cathelicidin LL-37/hCAP-18 originate from neutrophils. β-Defensins and LL-37/hCAP-18 are produced by the respiratory epithelium and the alveolar macrophage and secreted into the airway surface fluid. Beside their direct antimicrobial function, antimicrobial peptides have multiple roles as mediators of inflammation with effects on epithelial and inflammatory cells, influencing such diverse processes as proliferation, immune induction, wound healing, cytokine release, chemotaxis, protease-antiprotease balance, and redox homeostasis. Further, antimicrobial peptides qualify as prototypes of innovative drugs that might be used as antibiotics, anti-lipopolysaccharide drugs, or modifiers of inflammation

Antimicrobial proteins and polypeptides in pulmonary innate defence

Inspired air contains a myriad of potential pathogens, pollutants and inflammatory stimuli. In the normal lung, these pathogens are rarely problematic. This is because the epithelial lining fluid in the lung is rich in many innate immunity proteins and peptides that provide a powerful anti-microbial screen. These defensive proteins have anti-bacterial, anti- viral and in some cases, even anti-fungal properties. Their antimicrobial effects are as diverse as inhibition of biofilm formation and prevention of viral replication. The innate immunity proteins and peptides also play key immunomodulatory roles. They are involved in many key processes such as opsonisation facilitating phagocytosis of bacteria and viruses by macrophages and monocytes. They act as important mediators in inflammatory pathways and are capable of binding bacterial endotoxins and CPG motifs. They can also influence expression of adhesion molecules as well as acting as powerful anti-oxidants and anti-proteases. Exciting new antimicrobial and immunomodulatory functions are being elucidated for existing proteins that were previously thought to be of lesser importance. The potential therapeutic applications of these proteins and peptides in combating infection and preventing inflammation are the subject of ongoing research that holds much promise for the future

Determination of Beta-Defensin Genomic Copy Number in Different Populations: A Comparison of Three Methods

There have been conflicting reports in the literature on association of gene copy number with disease, including CCL3L1 and HIV susceptibility, and β-defensins and Crohn's disease. Quantification of precise gene copy numbers is important in order to define any association of gene copy number with disease. At present, real-time quantitative PCR (QPCR) is the most commonly used method to determine gene copy number, however the Paralogue Ratio Test (PRT) is being used in more and more laboratories.In this study we compare a Pyrosequencing-based Paralogue Ratio Test (PPRT) for determining beta-defensin gene copy number with two currently used methods for gene copy number determination, QPCR and triplex PRT by typing five different cohorts (UK, Danish, Portuguese, Ghanaian and Czech) of DNA from a total of 576 healthy individuals. We found a systematic measurement bias between DNA cohorts revealed by QPCR, but not by the PRT-based methods. Using PRT, copy number ranged from 2 to 9 copies, with a modal copy number of 4 in all populations.QPCR is very sensitive to quality of the template DNA, generating systematic biases that could produce false-positive or negative disease associations. Both triplex PRT and PPRT do not show this systematic bias, and type copy number within the correct range, although triplex PRT appears to be a more precise and accurate method to type beta-defensin copy number

Dendritic Cells Exposed to MVA-Based HIV-1 Vaccine Induce Highly Functional HIV-1-Specific CD8+ T Cell Responses in HIV-1-Infected Individuals

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8+ T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8+ T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1β, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4+ T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B

Integrating forest simulation models and spatial-temporal interactive visualisation for decision making at landscape level

The article represents an attempt to integrate long-term forest ecosystem modelling with modern techniques of exploratory data analysis. The idea of the integration was to build up a prototype system for forestry decision-making at landscape (forest enterprise) level to support the spatially oriented tasks arising from Criteria & Indicators (C&I) of Sustainable Forest Management (SFM). A model test was performed on a small forest plot consisting of various stands (forest inventory compartments) with two scenarios of silvicultural regimes. A combined spatially explicit forest simulation model EFIMOD 2 and the DESCARTES software system designed to support visual exploration of spatially referenced data were used in the experiment. The visualisation of simulation results on a sequence of interactive maps. It also allows direct representation of time series and spatial patterns of forest dynamics in a graphical form, and analysis of the dynamical trends under various silvicultural regimes. The diversity of ecosystem reactions in various stands was explored, and the possibilities for spatial combination of various strategies and zoning of the forest area were tested. We are sure there is a need to create a new, user-friendly modelling system integrating forest ecosystem models with exploratory data visualisation for methodologically easy and expressive decision-making based on expert evaluation and a long-term simulation at the forest enterprise or landscape level

MODELING OF KINEMATICS OF A PLASTIC SHAPING AT CALIBRATION OF A THIN-WALLED PRECISION PIPE SINKING

Summary. The mathematical model of kinematics of a plastic shaping at the sinking of a thin-walled precision pipe applied to calibration of the ends of the unified elements of the pipeline of aircraft from titanic alloys and corrosion-resistant steel before assembly to the route by means of automatic argon-arc welding of ring joints is developed. For modeling, the power criterion of stability with use of kinematic possible fields of speeds is applied to receiving the top assessment of effort of deformation. The developed model of kinematics of a plastic current allows to receive power parameters of the main condition of process of calibration by sinking and can be used for the solution of a task on stability of process of deformation by results of comparison of power (power) parameters for the main (steady) and indignant states. Modeling is made in cylindrical system of coordinates by comparison of options of kinematic possible fields of the speeds of a current meeting a condition of incompressibility and kinematic regional conditions. The result of the modeling was selected discontinuous field of high-speed, in which the decrease outer radius (R) occurs only by increasing the thickness of the pipe wall (t). For this option the size of pressure of sinking had the smallest value, therefore the chosen field of speeds closely to the valid. It is established that with increase in a step of giving 1 at calibration by the multisector tool the demanded pressure of sinking of q decreases. At an identical step of giving 1 pipe with the smaller relative thickness of (t/r) needs to be calibrated the smaller pressure of sinking. With increase of a limit of fluidity at shift of material of pipe preparation pressure of sinking of (q) increases