Diagnosing Emerging Fungal Threats: A One Health Perspective

Emerging fungal pathogens are a growing threat to global health, ecosystems, food security, and the world economy. Over the last century, environmental change and globalized transport, twinned with the increasing application of antifungal chemical drugs have led to increases in outbreaks of fungal diseases with sometimes catastrophic effects. In order to tackle contemporary epidemics and predemic threats, there is a pressing need for a unified approach in identification and monitoring of fungal pathogens. In this paper, we discuss current high throughput technologies, as well as new platforms capable of combining diverse data types to inform practical epidemiological strategies with a focus on emerging fungal pathogens of wildlife

Comparative efficacy of two poeciliid fish in indoor cement tanks against chikungunya vector Aedes aegypti in villages in Karnataka, India

<p>Abstract</p> <p>Background</p> <p>In 2006, severe outbreaks of <it>Aedes aegypti</it>-transmitted chikungunya occurred in villages in Karnataka, South India. We evaluated the effectiveness of combined information, education and communication (IEC) campaigns using two potential poeciliid larvivorous fish guppy (<it>Poecilia reticulata</it>) and mosquitofish (<it>Gambusia affinis</it>), in indoor cement tanks for <it>Aedes </it>larval control.</p> <p>Methods</p> <p>Trials were conducted in two villages (Domatmari and Srinivaspura) in Tumkur District from March to May 2006 for <it>Poecilia </it>and one village (Balmanda) in Kolar District from July to October 2006 for <it>Gambusia</it>. A survey on knowledge, attitude and practice (KAP) on chikungunya was initially conducted and IEC campaigns were performed before and after fish release in Domatmari (IEC alone, followed by IEC + <it>Poecilia</it>) and Balmanda (IEC + <it>Gambusia</it>). In Srinivaspura, IEC was not conducted. Larval surveys were conducted at the baseline followed by one-week and one-month post-intervention periods. The impact of fish on <it>Aedes </it>larvae and disease was assessed based on baseline and post-intervention observations.</p> <p>Results</p> <p>Only 18% of respondents knew of the role of mosquitoes in fever outbreaks, while almost all (<it>n </it>= 50 each) gained new knowledge from the IEC campaigns. In Domatmari, IEC alone was not effective (OR 0.54; <it>p </it>= 0.067). Indoor cement tanks were the most preferred <it>Ae. aegypti </it>breeding habitat (86.9%), and had a significant impact on <it>Aedes </it>breeding (Breteau Index) in all villages in the one-week period (<it>p </it>< 0.001). In the one-month period, the impact was most sustained in Domatmari (OR 1.58, <it>p </it>< 0.001) then Srinivaspura (OR 0.45, <it>p </it>= 0.063) and Balmanda (OR 0.51, <it>p </it>= 0.067). After fish introductions, chikungunya cases were reduced by 99.87% in Domatmari, 65.48% in Srinivaspura and 68.51% in Balmanda.</p> <p>Conclusions</p> <p><it>Poecilia </it>exhibited greater survival rates than <it>Gambusia </it>(86.04 <it>vs</it>.16.03%) in cement tanks. Neither IEC nor <it>Poecilia </it>alone was effective against <it>Aedes </it>(<it>p </it>> 0.05). We conclude that <it>Poecilia </it>+ IEC is an effective intervention strategy. The operational cost was 0.50 (US$0.011, 1 US$= 47) per capita per application. Proper water storage practices, focused IEC with <it>Poecilia </it>introductions and vector sanitation involving the local administration and community, is suggested as the best strategy for <it>Aedes </it>control.</p

Accreting Neutron Stars in Low-Mass X-Ray Binary Systems

Using the Rossi X-ray Timing Explorer (RossiXTE), astronomers have discovered that disk-accreting neutron stars with weak magnetic fields produce three distinct types of high-frequency X-ray oscillations. These oscillations are powered by release of the binding energy of matter falling into the strong gravitational field of the star or by the sudden nuclear burning of matter that has accumulated in the outermost layers of the star. The frequencies of the oscillations reflect the orbital frequencies of gas deep in the gravitational field of the star and/or the spin frequency of the star. These oscillations can therefore be used to explore fundamental physics, such as strong-field gravity and the properties of matter under extreme conditions, and important astrophysical questions, such as the formation and evolution of millisecond pulsars. Observations using RossiXTE have shown that some two dozen neutron stars in low-mass X-ray binary systems have the spin rates and magnetic fields required to become millisecond radio-emitting pulsars when accretion ceases, but that few have spin rates above about 600 Hz. The properties of these stars show that the paucity of spin rates greater than 600 Hz is due in part to the magnetic braking component of the accretion torque and to the limited amount of angular momentum that can be accreted in such systems. Further study will show whether braking by gravitational radiation is also a factor. Analysis of the kilohertz oscillations has provided the first evidence for the existence of the innermost stable circular orbit around dense relativistic stars that is predicted by strong-field general relativity. It has also greatly narrowed the possible descriptions of ultradense matter.Comment: 22 pages, 7 figures, updated list of sources and references, to appear in "Short-period Binary Stars: Observation, Analyses, and Results", eds. E.F. Milone, D.A. Leahy, and D. Hobill (Dordrecht: Springer, http://www.springerlink.com

The Effective Fragment Molecular Orbital Method for Fragments Connected by Covalent Bonds

We extend the effective fragment molecular orbital method (EFMO) into treating fragments connected by covalent bonds. The accuracy of EFMO is compared to FMO and conventional ab initio electronic structure methods for polypeptides including proteins. Errors in energy for RHF and MP2 are within 2 kcal/mol for neutral polypeptides and 6 kcal/mol for charged polypeptides similar to FMO but obtained two to five times faster. For proteins, the errors are also within a few kcal/mol of the FMO results. We developed both the RHF and MP2 gradient for EFMO. Compared to ab initio, the EFMO optimized structures had an RMSD of 0.40 and 0.44 {\AA} for RHF and MP2, respectively.Comment: Revised manuscrip

Radiative contribution to neutrino masses and mixing in μν\mu\nuSSM

In an extension of the minimal supersymmetric standard model (popularly known as the $\mu\nu$SSM), three right handed neutrino superfields are introduced to solve the $\mu$-problem and to accommodate the non-vanishing neutrino masses and mixing. Neutrino masses at the tree level are generated through $R-$parity violation and seesaw mechanism. We have analyzed the full effect of one-loop contributions to the neutrino mass matrix. We show that the current three flavour global neutrino data can be accommodated in the $\mu\nu$SSM, for both the tree level and one-loop corrected analyses. We find that it is relatively easier to accommodate the normal hierarchical mass pattern compared to the inverted hierarchical or quasi-degenerate case, when one-loop corrections are included.Comment: 51 pages, 14 figures (58 .eps files), expanded introduction, other minor changes, references adde

Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

<p>Abstract</p> <p>Background</p> <p>Intravenous (IV) artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe.</p> <p>Methods</p> <p>Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated.</p> <p>Results</p> <p>Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%). The mean time to 50% parasite clearance (PCT50), 90% and 99% were 4.4 hours (3.9 - 5.2), 14.8 hours (13.0 - 17.2), and 29.5 hours (25.9 - 34.4) respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain.</p> <p>Conclusions</p> <p>Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment.</p> <p>Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.</p

Low-molecular-weight cyclin E: the missing link between biology and clinical outcome

Cyclin E, a key mediator of transition during the G(1)/S cellular division phase, is deregulated in a wide variety of human cancers. Our group recently reported that overexpression and generation of low-molecular-weight (LMW) isoforms of cyclin E were associated with poor clinical outcome among breast cancer patients. However, the link between LMW cyclin E biology in mediating a tumorigenic phenotype and clinical outcome is unknown. To address this gap in knowledge, we assessed the role of LMW isoforms in breast cancer cells; we found that these forms of cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens in breast cancer. These findings suggest that high levels of LMW isoforms of cyclin E not only can predict failure to endocrine therapy but also are true prognostic indicators because of their influence on cell proliferation and genetic instability

A Common Carcinogen Benzo[a]pyrene Causes Neuronal Death in Mouse via Microglial Activation

BACKGROUND: Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels. CONCLUSIONS/SIGNIFICANCE: Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our study throws light on other health hazards that such pollutants may exert

The Role of Histone H4 Biotinylation in the Structure of Nucleosomes

Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp to the classical 147 bp length of nucleosomal DNA. Conclusions/Significance: The increase in nucleosomal DNA length is predicted to stabilize the association of DNA with histones and therefore to prevent nucleosomes from unwrapping. This provides a mechanistic explanation for the gene silencing associated with K12Bio-H4. The proposed single-molecule AFM approach will be instrumental for studying the effects of various epigenetic modifications of nucleosomes, in addition to biotinylation

World input-output network

Production systems, traditionally analyzed as almost independent national systems, are increasingly connected on a global scale. Only recently becoming available, the World Input-Output Database (WIOD) is one of the first efforts to construct the global multi-regional input-output (GMRIO) tables. By viewing the world input-output system as an interdependent network where the nodes are the individual industries in different economies and the edges are the monetary goods flows between industries, we analyze respectively the global, regional, and local network properties of the so-called world input-output network (WION) and document its evolution over time. At global level, we find that the industries are highly but asymmetrically connected, which implies that micro shocks can lead to macro fluctuations. At regional level, we find that the world production is still operated nationally or at most regionally as the communities detected are either individual economies or geographically well defined regions. Finally, at local level, for each industry we compare the network-based measures with the traditional methods of backward linkages. We find that the network-based measures such as PageRank centrality and community coreness measure can give valuable insights into identifying the key industries