The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P ≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P ≤0.05). In addition, lactoferrin (P ≤0.002), transferrin receptor (P ≤0.05) and solute carrier family 11A1 (P ≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Parliamentarians and corruption in Africa: the challenge of leadership and the practice of politics

This report, compiled on behalf of the African Parliamentary Network Against Corruption (APNAC), surveys the attitudes of African parliamentarians toward corruption. It is the first study of its kind to investigate the manner in which corruption impacts directly upon the political behaviour, practices and attitudes of those elected members sitting in parliaments across the continent. If the problems of corruption are to be tackled in the African continent, then the role of elected members of legislative assemblies will surely be a crucial factor.

PETS 2015: datasets and challenge

This paper presents the two datasets (ARENA and P5) and the challenge that form a part of the PETS 2015 workshop. The datasets consist of scenarios recorded by us- ing multiple visual and thermal sensors. The scenarios in ARENA dataset involve different staged activities around a parked vehicle in a parking lot in UK and those in P5 dataset involve different staged activities around the perimeter of a nuclear power plant in Sweden. The scenarios of each dataset are grouped into ‘Normal’, ‘Warning’ and ‘Alarm’ categories. The Challenge specifically includes tasks that account for different steps in a video understanding system: Low-Level Video Analysis (object detection and tracking), Mid-Level Video Analysis (‘atomic’ event detection) and High-Level Video Analysis (‘complex’ event detection). The evaluation methodology used for the Challenge includes well-established measures.

Tracking performance evaluation on PETS 2015 Challenge datasets

This paper presents a quantitative evaluation of a tracking system on PETS 2015 Challenge datasets using well-established performance measures. Using the existing tools, the tracking system implements an end-to-end pipeline that include object detection, tracking and post- processing stages. The evaluation results are presented on the provided sequences of both ARENA and P5 datasets of PETS 2015 Challenge. The results show an encouraging performance of the tracker in terms of accuracy but a greater tendency of being prone to cardinality error and ID changes on both datasets. Moreover, the analysis show a better performance of the tracker on visible imagery than on thermal imagery.

PETS 2014: dataset and challenge

This paper describes the dataset and vision challenges that form part of the PETS 2014 workshop. The datasets are multisensor sequences containing different activities around a parked vehicle in a parking lot. The dataset scenarios were filmed from multiple cameras mounted on the vehicle itself and involve multiple actors. In PETS2014 workshop, 22 acted scenarios are provided of abnormal behaviour around the parked vehicle. The aim in PETS 2014 is to provide a standard benchmark that indicates how detection, tracking, abnormality and behaviour analysis systems perform against a common database. The dataset specifically addresses several vision challenges corresponding to different steps in a video understanding system: Low-Level Video Analysis (object detection and tracking), Mid-Level Video Analysis (‘simple’ event detection: the behaviour recognition of a single actor) and High-Level Video Analysis (‘complex’ event detection: the behaviour and interaction recognition of several actors).

Clubroot (Plasmodiophora brassicae Woronin): an agricultural and biological challenge worldwide

Clubroot disease and the causal microbe Plasmodiophora brassicae offer abundant challenges to agriculturists and biological scientists. This microbe is well fitted for the environments which it inhabits. Plasmodiophora brassicae exists in soil as microscopic well protected resting spores and then grows actively and reproduces while shielded inside the roots of host plants. The pathogen is active outside the host for only short periods. Consequently, scientific studies are made challenging by the biological context of the host and pathogen and the technology required to investigate and understand that relationship. Controlling clubroot disease is a challenge for farmers, crop consultants and plant pathology practitioners because of the limited options which are available. Full symptom expression happens solely in members of the Brassicaceae family. Currently, only a few genes expressing strong resistance to P. brassicae are known and readily available. Agrochemical control is similarly limited by difficulties in molecule formulation which combines efficacy with environmental acceptability. Manipulation of husbandry encouraging improvements in soil structure, texture, nutrient composition and moisture content can reduce populations of P. brassicae. Integrating such strategies with rotation and crop management will reduce but not eliminate this disease. There are indications that forms of biological competition may be mobilised as additions to integrated control strategies. The aim of this review is to chart key themes in the development of scientific biological understanding of this host-pathogen relationship by offering signposts to grapple with clubroot disease which devastates crops and their profitability. Particular attention is given to the link between soil and nutrient chemistry and activity of this microbe.

The status and challenge of global fire modelling

Biomass burning impacts vegetation dynamics, biogeochemical cycling, atmospheric chemistry, and climate, with sometimes deleterious socio-economic impacts. Under future climate projections it is often expected that the risk of wildfires will increase. Our ability to predict the magnitude and geographic pattern of future fire impacts rests on our ability to model fire regimes, either using well-founded empirical relationships or process-based models with good predictive skill. A large variety of models exist today and it is still unclear which type of model or degree of complexity is required to model fire adequately at regional to global scales. This is the central question underpinning the creation of the Fire Model Intercomparison Project - FireMIP, an international project to compare and evaluate existing global fire models against benchmark data sets for present-day and historical conditions. In this paper we summarise the current state-of-the-art in fire regime modelling and model evaluation, and outline what essons may be learned from FireMIP.

A carbon isotope challenge to the snowball Earth

The snowball Earth hypothesis postulates that the planet was entirely covered by ice for millions of years in the Neoproterozoic era, in a self-enhanced glaciation caused by the high albedo of the ice-covered planet. In a hard-snowball picture, the subsequent rapid unfreezing resulted from an ultra-greenhouse event attributed to the buildup of volcanic carbon dioxide (CO(2)) during glaciation(1). High partial pressures of atmospheric CO(2) (p(CO2); from 20,000 to 90,000 p. p. m. v.) in the aftermath of the Marinoan glaciation (similar to 635 Myr ago) have been inferred from both boron and triple oxygen isotopes(2,3). These p(CO2) values are 50 to 225 times higher than present-day levels. Here, we re-evaluate these estimates using paired carbon isotopic data for carbonate layers that cap Neoproterozoic glacial deposits and are considered to record post-glacial sea level rise(1). The new data reported here for Brazilian cap carbonates, together with previous ones for time-equivalent units(4-8), provide p(CO2) estimates lower than 3,200 p. p. m. v.-and possibly as low as the current value of similar to 400 p. p. m. v. Our new constraint, and our reinterpretation of the boron and triple oxygen isotope data, provide a completely different picture of the late Neoproterozoic environment, with low atmospheric concentrations of carbon dioxide and oxygen that are inconsistent with a hard-snowball Earth.

The challenge of maintaining Atlantic forest biodiversity: A multi-taxa conservation assessment of specialist and generalist species in an agro-forestry mosaic in southern Bahia

Recent developments have highlighted the importance of forest amount at large spatial scales and of matrix quality for ecological processes in remnants. These developments, in turn, suggest the potential for reducing biodiversity loss through the maintenance of a high percentage of forest combined with sensitive management of anthropogenic areas. We conducted a multi-taxa survey to evaluate the potential for biodiversity maintenance in an Atlantic forest landscape that presented a favorable context from a theoretical perspective (high proportion of mature forest partly surrounded by structurally complex matrices). We sampled ferns, butterflies, frogs, lizards, bats, small mammals and birds in interiors and edges of large and small mature forest remnants and two matrices (second-growth forests and shade cacao plantations), as well as trees in interiors of small and large remnants. By considering richness, abundance and composition of forest specialists and generalists, we investigated the biodiversity value of matrix habitats (comparing them with interiors of large remnants for all groups except tree), and evaluated area (for all groups) and edge effects (for all groups except trees) in mature forest remnants. our results suggest that in landscapes comprising high amounts of mature forest and low contrasting matrices: (1) shade cacao plantations and second-growth forests harbor an appreciable number of forest specialists; (2) most forest specialist assemblages are not affected by area or edge effects, while most generalist assemblages proliferate at edges of small remnants. Nevertheless, differences in tree assemblages, especially among smaller trees, Suggest that observed patterns are unlikely to be stable over time. (C) 2009 Elsevier Ltd. All rights reserved.

A DNA Vaccine Encoding the Enterohemorragic Escherichia coli Shiga-Like Toxin 2 A(2) and B Subunits Confers Protective Immunity to Shiga Toxin Challenge in the Murine Model

Production of verocytotoxin or Shiga-like toxin (Stx), particularly Stx2, is the basis of hemolytic uremic syndrome, a frequently lethal outcome for subjects infected with Stx2-producing enterohemorrhagic Escherichia coli (EHEC) strains. The toxin is formed by a single A subunit, which promotes protein synthesis inhibition in eukaryotic cells, and five B subunits, which bind to globotriaosylceramide at the surface of host cells. Host enzymes cleave the A subunit into the A(1) peptide, endowed with N-glycosidase activity to the 28S rRNA, and the A(2) peptide, which confers stability to the B pentamer. We report the construction of a DNA vaccine (pStx2 Delta AB) that expresses a nontoxic Stx2 mutated form consisting of the last 32 amino acids of the A(2) sequence and the complete B subunit as two nonfused polypeptides. Immunization trials carried out with the DNA vaccine in BALB/c mice, alone or in combination with another DNA vaccine encoding granulocyte-macrophage colony-stimulating factor, resulted in systemic Stx-specific antibody responses targeting both A and B subunits of the native Stx2. Moreover, anti-Stx2 antibodies raised in mice immunized with pStx2 Delta AB showed toxin neutralization activity in vitro and, more importantly, conferred partial protection to Stx2 challenge in vivo. The present vector represents the second DNA vaccine so far reported to induce protective immunity to Stx2 and may contribute, either alone or in combination with other procedures, to the development of prophylactic or therapeutic interventions aiming to ameliorate EHEC infection-associated sequelae.

Why Implementing History and Philosophy in School Science Education is a Challenge: An Analysis of Obstacles

Teaching and learning with history and philosophy of science (HPS) has been, and continues to be, supported by science educators. While science education standards documents in many countries also stress the importance of teaching and learning with HPS, the approach still suffers from ineffective implementation in school science teaching. In order to better understand this problem, an analysis of the obstacles of implementing HPS into classrooms was undertaken. The obstacles taken into account were structured in four groups: 1. culture of teaching physics, 2. teachers` skills, epistemological and didactical attitudes and beliefs, 3. institutional framework of science teaching, and 4. textbooks as fundamental didactical support. Implications for more effective implementation of HPS are presented, taking the social nature of educational systems into account.

Excited Electronic States, Transition Probabilities, and Radiative Lifetimes of CAs: A Theoretical Contribution and Challenge to Experimentalists

High-level CASSCF/MRCI calculations with a quintuple-zeta quality basis set are reported by characterizing for the first time a manifold of electronic states of the CAs radical yet to be investigated experimentally. Along with the potential energy curves and the associated spectroscopic constants, the dipole moment functions for selected electronic states as well as the transition dipole moment functions for the most relevant electronic transitions are also presented. Estimates of radiative transition probabilities and lifetimes complement this investigation, which also assesses the effect of spin-orbit interaction on the A (2)Pi state. Whenever pertinent, comparisons of similarities and differences with the isovalent CN and CP radicals are made.