Human platelet activation by Escherichia coli: roles for FcγRIIA and integrin αIIbβ3

Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet–bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood. While the IgG receptor FcγRIIA has a key role in platelet response to various Gram-positive species, its role in activation to Gram-negative bacteria is poorly defined. This study aimed to investigate the molecular mechanisms of human platelet activation by E. coli, including the potential role of FcγRIIA. Using light-transmission aggregometry, measurements of ATP release and tyrosine-phosphorylation, we investigated the ability of two E. coli clinical isolates to activate platelets in plasma, in the presence or absence of specific receptors and signaling inhibitors. Aggregation assays with washed platelets supplemented with IgGs were performed to evaluate the requirement of this plasma component in activation. We found a critical role for the immune receptor FcγRIIA, αIIbβ3, and Src and Syk tyrosine kinases in platelet activation in response to E. coli. IgG and αIIbβ3 engagement was required for FcγRIIA activation. Moreover, feedback mediators adenosine 5’-diphosphate (ADP) and thromboxane A₂ (TxA₂) were essential for platelet aggregation. These findings suggest that human platelet responses to E. coli isolates are similar to those induced by Gram-positive organisms. Our observations support the existence of a central FcγRIIA-mediated pathway by which human platelets respond to both Gram-negative and Gram-positive bacteria

One-Loop MHV Amplitudes in Supersymmetric Gauge Theories

Using CSW rules for constructing scalar Feynman diagrams from MHV vertices, we compute the contribution of $\mathcal {N}=1$ chiral multiplet to one-loop MHV gluon amplitude. The result agrees with the one obtained previously using unitarity-based methods, thereby demonstrating the validity of the MHV-diagram technique, in the case of one-loop MHV amplitudes, for all massless supersymmetric theories.Comment: 20 pages, 5 figure

Instanton test of non-supersymmetric deformations of the AdS_5 x S^5

We consider instanton effects in a non-supersymmetric gauge theory obtained by marginal deformations of the N=4 SYM. This gauge theory is expected to be dual to type IIB string theory on the AdS_5 times deformed-S^5 background. From an instanton calculation in the deformed gauge theory we extract the prediction for the dilaton-axion field \tau in dual string theory. In the limit of small deformations where the supergravity regime is valid, our instanton result reproduces the expression for \tau of the supergravity solution found by Frolov.Comment: 15 page

Reefs at Risk: A Map-Based Indicator of Threats to the Worlds Coral Reefs

This report presents the first-ever detailed, map-based assessment of potential threats to coral reef ecosystems around the world. "Reefs at Risk" draws on 14 data sets (including maps of land cover, ports, settle-ments, and shipping lanes), information on 800 sites known to be degraded by people, and scientific expertise to model areas where reef degradation is predicted to occur, given existing human pressures on these areas. Results are an indicator of potential threat (risk), not a measure of actual condition. In some places, particularly where good management is practiced, reefs may be at risk but remain relatively healthy. In others, this indicator underestimates the degree to which reefs are threatened and degraded.Our results indicate that:Fifty-eight percent of the world's reefs are poten-tially threatened by human activity -- ranging from coastal development and destructive fishing practices to overexploitation of resources, marine pollution, and runoff from inland deforestation and farming.Coral reefs of Asia (Southeastern); the most species-rich on earth, are the most threatened of any region. More than 80 percent are at risk (undermedium and high potential threat), and over half are at high risk, primarily from coastal development and fishing-related pressures.Overexploitation and coastal development pose the greatest potential threat of the four risk categories considered in this study. Each, individually, affects a third of all reefs.The Pacific, which houses more reef area than any other region, is also the least threatened. About 60 percent of reefs here are at low risk.Outside of the Pacific, 70 percent of all reefs are at risk.At least 11 percent of the world's coral reefs contain high levels of reef fish biodiversity and are under high threat from human activities. These "hot spot" areas include almost all Philippine reefs, and coral communities off the coasts of Asia, the Comoros, and the Lesser Antilles in the Caribbean.Almost half a billion people -- 8 percent of the total global population -- live within 100 kilometers of a coral reef.Globally, more than 400 marine parks, sanctuaries, and reserves (marine protected areas) contain coral reefs. Most of these sites are very small -- more than 150 are under one square kilometer in size. At least 40 countries lack any marine protected areas for conserving their coral reef systems

The role of marine reserves in achieving sustainable fisheries (One contribution of 15 to a Theme Issue 'Fisheries: a Future?')

Many fishery management tools currently in use have conservation value. They are designed to maintain stocks of commercially important species above target levels. However, their limitations are evident from continuing declines in fish stocks throughout the world. We make the case that to reverse fishery declines, safeguard marine life and sustain ecosystem processes, extensive marine reserves that are off limits to fishing must become part of the management strategy. Marine reserves should be incorporated into modern fishery management because they can achieve many things that conventional tools cannot. Only complete and permanent protection from fishing can protect the most sensitive habitats and vulnerable species. Only reserves will allow the development of natural, extended age structures of target species, maintain their genetic variability and prevent deleterious evolutionary change from the effects of fishing. Species with natural age structures will sustain higher rates of reproduction and will be more resilient to environmental variability. Higher stock levels maintained by reserves will provide insurance against management failure, including risk-prone quota setting, provided the broader conservation role of reserves is firmly established and legislatively protected. Fishery management measures outside protected areas are necessary to complement the protection offered by marine reserves, but cannot substitute for it

Genetic analysis of radiation resistance in Haloferax volcanii

Archaea,considered as the third domain of life alongside bacteria and eukaryotes, represent a highly diverse group of organisms. Attention to archaeal DNA repair pathways has been considerable for a long time and many archaeal species inhabit extreme environmental niches where there is a higher rate of genomic insult. It is therefore thought that such archaea possess efficient and robust novel DNA repair pathways, allowing survival in such conditions. Such extreme conditions can also be found beyond Earth, such as on the surface of Mars and investigation into DNA repair in the archaea represents a pivotal stepping stone to understanding how organisms adapt to “Martian” conditions. In the work presented here, the gene encoding a XerCD-like integrase, found within the integrated prophage on the main chromosome of Haloferax volcanii was isolated from a genomic library and overexpression leads to increased resistance to genotoxic stress imposed by ultraviolet light and mitomycin C. Deletion of this gene does not impact the growth rate or sensitivity to DNA damaging agents, likely due to the presence of an additional eleven homologs within the genome. Deletion of the entire prophage region does not delete all XerCD homologs, yet shows an even larger increase in cell survival after UV and MMC treatment. Genetic analysis suggests that XerCD may interact, directly or indirectly, with UvrC as overexpression of XerCD somewhat mitigates the UV sensitivity seen in a UvrC deleted strain. The defect is not fully complemented, so further study is required. Previous data has shown that various XerCD-like integrases are upregulated in the presence of MMC. Real-time PCR carried out here indicates that phage induction may occur when cells are treated with DNA damaging agents, which may contribute to the cell death seen, and therefore strains deleted for the integrated prophage may be more beneficial to use for DNA damaging assays due to increased cellular survival. Replication Protein A transcripts are upregulated in response to MMC, aiding in interstrand crosslink repair. The interplay between XerCD-like integrases, that usually function in DNA replication, and DNA repair warrants further study

Exploring the Psychopysiological Indices of Perceived Effort and its Self-Regulation

Effort involves the application of physical and mental resources towards a task. Individuals perceive effort during task engagement like exercise with a conscious sensation of how hard, heavy, and strenuous the exercise consciously feels to drive the working muscles and for breathing. Accordingly, individuals' decisions are thought to be guided by their perceived effort. In turn, there are numerous psychophysiological characteristics that underpin the perceived effort phenomenon which can also play a role in the overall decision-making processes and self-regulation of behaviour. However, it is often difficult to capture the underlying mechanisms of decision-making processes due to their erratic and complex nature. Consequently, there is scant literature on the psychophysiological indices of set perceived effort intensities and underlying decision-making processes during self-regulation of perceived effort. Yet, a small sample of studies have demonstrated that concurrent mixed-methods/process-tracing approaches can delve more into complex decision-making processes involved with regulating perceived effort and exercise behaviour. Subsequently, the main aim of the present thesis was to explore the psychophysiological indices of perceived effort and its self-regulation. This thesis comprises three separate studies. In Study 1, the reliability of a novel fixed perceived effort cycling task was investigated. Results demonstrated that a novel fixed perceived effort trial that corresponded ratings of perceived effort to a known physiological threshold was reliably produced over numerous bouts and elicited a consistent psychophysiological response for each perceived effort intensity. A following study (Study 2, Part A) also probed the psychophysiological responses associated with two intensities of fixed perceived effort. During these studies it appeared that physical outputs at a set perceived effort intensity would decrease over time to maintain the same perception of effort. Meanwhile, certain psychophysiological markers showed characteristic increases (e.g., heart rate) or decreases (e.g., affective valence) as the fixed perceived effort exercise progressed. As a result, specific intensities of perceived effort appear to exhibit different power output and psychophysiological responses in terms of magnitude and changes over time. This could possibly then be linked to different ways that perceived effort is self-regulated. It was also of interest how individuals self-regulated during fixed perceived effort exercise. To achieve this, Study 2 utilised a think aloud protocol to understand the behavioural and cognitive self-regulatory strategies that were used by participants at different fixed perceived effort intensities (Part A) as well as any differences in self-regulation between experienced and inexperienced cyclists (Part B). Within Part A, it was found that there was a greater change in power output during the higher intensity fixed perceived effort cycle, signifying a greater amount of behavioural self-regulation. Furthermore, the activation of cognitive strategies was also greater in the higher intensity fixed perceived effort task. When assessing differences between experience levels of participants, there were no significant differences in power output or major secondary themes of the think aloud protocol suggesting participants of any experience level may self-regulate perceived effort similarly. However, closer examination of the primary themes from the think aloud data suggest experience level may affect the cognitive self-regulatory strategies that are used during a prolonged fixed perceived effort intensity exercise. Finally, this thesis then explored any changes in self-regulation of perceived effort after an intervention which involved experimentally induced muscle pain. In addition, this study also incorporated the use of functional near infrared spectroscopy to assess the cognitive effort applied to activate cognitive self-regulation strategies during fixed perceived effort exercise. It was found that the presence of elevated muscle pain due to an intramuscular hypertonic saline injection cause a significantly lower power output than an isotonic placebo-control condition. In addition, near infrared spectroscopy data showed a greater change in deoxyhaemoglobin between condition suggesting a greater use of cognitive self-regulatory strategies as part of executive function when experiencing elevated muscle pain compared to a placebo-control. Overall, this thesis firstly found a novel fixed perceived effort exercise to be reliable. Using this task paradigm, additional studies show that specific intensities of perceived effort seem to elicit different power output and psychophysiological responses in terms of magnitude (e.g., higher/lower between intensities) and changes over time (condition x time interactions). Subsequently, data concerning the self-regulation of perceived effort shows that participants employ a mixture of behavioural (i.e., changing power output) and cognitive (i.e., engaging in reappraisal and/or self-talk) strategies to self-regulate perceived effort. In addition, there was a difference in self-regulatory strategies between conditions which involved elevated muscle pain (hypertonic saline injection) or a no elevated muscle pain (isotonic saline injection). Therefore, the self-regulation of perceived effort is likely context dependent and there are also likely to be some individual preferences towards how perceived effort is self-regulated

Genetic analysis of radiation resistance in Haloferax volcanii

Archaea,considered as the third domain of life alongside bacteria and eukaryotes, represent a highly diverse group of organisms. Attention to archaeal DNA repair pathways has been considerable for a long time and many archaeal species inhabit extreme environmental niches where there is a higher rate of genomic insult. It is therefore thought that such archaea possess efficient and robust novel DNA repair pathways, allowing survival in such conditions. Such extreme conditions can also be found beyond Earth, such as on the surface of Mars and investigation into DNA repair in the archaea represents a pivotal stepping stone to understanding how organisms adapt to “Martian” conditions. In the work presented here, the gene encoding a XerCD-like integrase, found within the integrated prophage on the main chromosome of Haloferax volcanii was isolated from a genomic library and overexpression leads to increased resistance to genotoxic stress imposed by ultraviolet light and mitomycin C. Deletion of this gene does not impact the growth rate or sensitivity to DNA damaging agents, likely due to the presence of an additional eleven homologs within the genome. Deletion of the entire prophage region does not delete all XerCD homologs, yet shows an even larger increase in cell survival after UV and MMC treatment. Genetic analysis suggests that XerCD may interact, directly or indirectly, with UvrC as overexpression of XerCD somewhat mitigates the UV sensitivity seen in a UvrC deleted strain. The defect is not fully complemented, so further study is required. Previous data has shown that various XerCD-like integrases are upregulated in the presence of MMC. Real-time PCR carried out here indicates that phage induction may occur when cells are treated with DNA damaging agents, which may contribute to the cell death seen, and therefore strains deleted for the integrated prophage may be more beneficial to use for DNA damaging assays due to increased cellular survival. Replication Protein A transcripts are upregulated in response to MMC, aiding in interstrand crosslink repair. The interplay between XerCD-like integrases, that usually function in DNA replication, and DNA repair warrants further study