Slaving and release in co-infection control

Background Animal and human infection with multiple parasite species is the norm rather than the exception, and empirical studies and animal models have provided evidence for a diverse range of interactions among parasites. We demonstrate how an optimal control strategy should be tailored to the pathogen community and tempered by species-level knowledge of drug sensitivity with use of a simple epidemiological model of gastro-intestinal nematodes. Methods We construct a fully mechanistic model of macroparasite co-infection and use it to explore a range of control scenarios involving chemotherapy as well as improvements to sanitation. Results Scenarios are presented whereby control not only releases a more resistant parasite from antagonistic interactions, but risks increasing co-infection rates, exacerbating the burden of disease. In contrast, synergisms between species result in their becoming epidemiologically slaved within hosts, presenting a novel opportunity for controlling drug resistant parasites by targeting co-circulating species. Conclusions Understanding the effects on control of multi-parasite species interactions, and vice versa, is of increasing urgency in the advent of integrated mass intervention programmes.

The pollution release and transfer register system in the U.S. and Japan : an analysis of productivity

This study analyzes Total Factor Productivity (TFP), which includes all categories of productivity. Our measure investigates productivity in the context of the provision and dissemination of environmental information policies. We investigated data on the emission of toxic chemical substances for the U.S. and Japanese manufacturing firms, including 386 firms for the period 1999-2007 and 466 firms for the period 2001-2008. The results show that productivity improved in all nine industrial sectors and that pollution levels were high in the U.S. and Japan from 2001 to 2007. In particular, the electronics industry improved rapidly after 2002 in both countries, which may be attributed to the enforcement of RoHS and the REACH directive in Europe. As a result of these stringent policies on toxic chemical emissions, the U.S. and Japanese firms, many of which export to the European market, have strong incentives to reduce their toxic chemical emissions.

Preparation and in vitro release of zein microparticles loaded with prednisolone for oral delivery

Zein has been proposed as a polymer for targeted-drug delivery via the oral route. Zein microparticles were loaded with prednisolone and evaluated as an oral delivery system. Microparticles were formulated using phase separation. Starting quantities of zein and prednisolone, along with the agitation method and temperature were found to significantly impact drug loading and loading efficiency. Vortex mixing produced the highest drug loading and loading efficiency. Drug release was measured in simulated conditions of the stomach and small intestine using the microparticles made with the method that best improved drug loading. In simulated stomach and small intestine conditions, prednisolone release reached almost 70 over 3 and 4h, respectively. While a clinically relevant dose may be delivered using c. 100mg of zein microparticles, prednisolone release from the microparticles indicates that they may not be suited as a controlled-or targeted-delivery system.

MMP-14 is expressed in preeclamptic placentas and mediates release of soluble endoglin

Soluble endoglin is an anti-angiogenic protein that is released from the placenta and contributes to both maternal endothelial dysfunction and the clinical features of severe preeclampsia. The mechanism through which soluble endoglin is released from the placenta is currently unknown; however, recent work in colorectal cancer identified matrix metalloproteinase 14 (MMP-14) as the cleavage protease of endoglin. To determine whether this is also the mechanism responsible for soluble endoglin release in preeclampsia, we investigated the expression of MMP-14 within the placenta and the effects of its inhibition on soluble endoglin release. Placentas were obtained from severe, early onset preeclamptic pregnancies (n = 8) and gestationally matched preterm controls (n = 8). MMP-14 was predominately localized to the syncytiotrophoblast. Results from a proximity ligation assay showed protein interactions between endogenous MMP-14 and endoglin within the preeclamptic placenta. To demonstrate that this interaction produces soluble endoglin, we treated trophoblastic BeWo cells with either a broad-spectrum MMP inhibitor (GM6001) or MMP-14 siRNA. Both treatments produced a decrease in soluble endoglin (P ≤ 0.05). Treatment of mice bearing BeWo xenografts with GM6001 decreased circulating soluble endoglin levels in mouse serum (P ≤ 0.05). These findings indicate that MMP-14 is the likely cleavage protease of endoglin in the setting of preeclampsia. This approach provides a novel method for the development of potential therapeutics to reduce circulating soluble endoglin and ameliorate the clinical features of severe preeclampsia.

Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens

BACKGROUND AND PURPOSE Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline’s effects on ethanol consumption. EXPERIMENTAL APPROACH Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV). KEY RESULTS Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc. CONCLUSION AND IMPLICATIONS Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline’s effects on ethanol consumption.

Accelerating taxonomic discovery through automated character extraction

This paper discusses the following key messages. Taxonomy is (and taxonomists are) more important than ever in times of global change. Taxonomic endeavour is not occurring fast enough: in 250 years since the creation of the Linnean Systema Naturae, only about 20% of Earth's species have been named. We need fundamental changes to the taxonomic process and paradigm to increase taxonomic productivity by orders of magnitude. Currently, taxonomic productivity is limited principally by the rate at which we capture and manage morphological information to enable species discovery. Many recent (and welcomed) initiatives in managing and delivering biodiversity information and accelerating the taxonomic process do not address this bottleneck. Development of computational image analysis and feature extraction methods is a crucial missing capacity needed to enable taxonomists to overcome the taxonomic impediment in a meaningful time frame. Copyright © 2009 Magnolia Press.

Cultural relativity as exchange : J.W. Lindt’s bush character and Aboriginal from The Grafton Album (circa 1872)

J.W.Lindt’s Colonial man and Aborigine image from the GRAFTON ALBUM: “On chemistry and optics all does not depend, art must with these in triple union blend” (text from J.W. Lindt’s photographic backing card)...

Are there generalizable trends in the release of airborne synthetic clay nanoparticles from a jet milling process?

Despite recent efforts to assess the release of nanoparticles to the workplace during different nanotechnology activities, the existence of a generalizable trend in the particle release has yet to be identified. This study aimed to characterize the release of synthetic clay nanoparticles from a laboratory-based jet milling process by quantifying the variations arising from primary particle size and surface treatment of the material used, as well as the feed rate of the machine. A broad range of materials were used in this study, and the emitted particles mass (PM2.5) and number concentrations (PNC) were measured at the release source. Analysis of variance, followed by linear mixed-effects modeling, was applied to quantify the variations in PM2.5 and PNC of the released particles caused by the abovementioned factors. The results confirmed that using materials of different primary size and surface treatment affects the release of the particles from the same process by causing statistically-significant variations in PM2.5 and PNC. The interaction of these two factors should also be taken into account as it resulted in variations in the measured particles release properties. Furthermore, the feed rate of the milling machine was confirmed to be another influencing parameter. Although this research does not identify a specific pattern in the release of synthetic clay nanoparticles from the jet milling process generalizable to other similar settings, it emphasizes that each tested case should be handled individually in terms of exposure considerations.

Impaction of spray droplets on leaves: Influence of formulation and leaf character on shatter, bounce and adhesion

This paper combines experimental data with simple mathematical models to investigate the influence of spray formulation type and leaf character (wettability) on shatter, bounce and adhesion of droplets impacting with cotton, rice and wheat leaves. Impaction criteria that allow for different angles of the leaf surface and the droplet impact trajectory are presented; their predictions are based on whether combinations of droplet size and velocity lie above or below bounce and shatter boundaries. In the experimental component, real leaves are used, with all their inherent natural variability. Further, commercial agricultural spray nozzles are employed, resulting in a range of droplet characteristics. Given this natural variability, there is broad agreement between the data and predictions. As predicted, the shatter of droplets was found to increase as droplet size and velocity increased, and the surface became harder to wet. Bouncing of droplets occurred most frequently on hard to wet surfaces with high surface tension mixtures. On the other hand, a number of small droplets with low impact velocity were observed to bounce when predicted to lie well within the adhering regime. We believe this discrepancy between the predictions and experimental data could be due to air layer effects that were not taken into account in the current bounce equations. Other discrepancies between experiment and theory are thought to be due to the current assumption of a dry impact surface, whereas, in practice, the leaf surfaces became increasingly covered with fluid throughout the spray test runs.

Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

Clinoenstatite coatings have high bonding strength, bioactive ion release, and osteoimmunomodulatory effects that enhance in vivo osseointegration

A number of coating materials have been developed over past two decades seeking to improve the osseointegration of orthopedic metal implants. Despite the many candidate materials trialed, their low rate of translation into clinical applications suggests there is room for improving the current strategies for their development. We therefore propose that the ideal coating material(s) should possess the following three properties: (i) high bonding strength, (ii) release of functional ions, and (iii) favourable osteoimmunomodulatory effects. To test this proposal, we developed clinoenstatite (CLT, MgSiO3), which as a coating material has high bonding strength, cytocompability and immunomodulatory effects that are favourable for in vivo osteogenesis. The bonding strength of CLT coatings was 50.1 ± 3.2 MPa, more than twice that of hydroxyapatite (HA) coatings, at 23.5 ± 3.5 MPa. CLT coatings released Mg and Si ions, and compared to HA coatings, induced an immunomodulation more conducive for osseointegration, demonstrated by downregurelation of pro-inflammatory cytokines, enhancement of osteogenesis, and inhibition of osteoclastogenesis. In vivo studies demonstrated that CLT coatings improved osseointegration with host bone, as shown by the enhanced biomechanical strength and increased de novo bone formation, when compared with HA coatings. These results support the notion that coating materials with the proposed properties can induce an in vivo environment better suited for osseointegration. These properties could, therefore, be fundamental when developing high-performance coating materials.

In situ investigation of explosive crystallization in a-Ge: Experimental determination of the interface response function using dynamic transmission electron microscopy

The crystallization of amorphous semiconductors is a strongly exothermic process. Once initiated the release of latent heat can be sufficient to drive a self-sustaining crystallization front through the material in a manner that has been described as explosive. Here, we perform a quantitative in situ study of explosive crystallization in amorphous germanium using dynamic transmission electron microscopy. Direct observations of the speed of the explosive crystallization front as it evolves along a laser-imprinted temperature gradient are used to experimentally determine the complete interface response function (i.e., the temperature-dependent front propagation speed) for this process, which reaches a peak of 16 m/s. Fitting to the Frenkel-Wilson kinetic law demonstrates that the diffusivity of the material locally/immediately in advance of the explosive crystallization front is inconsistent with those of a liquid phase. This result suggests a modification to the liquid-mediated mechanism commonly used to describe this process that replaces the phase change at the leading amorphous-liquid interface with a change in bonding character (from covalent to metallic) occurring in the hot amorphous material.

Plantar pressure distribution character in young female with mild hallux valgus wearing high-heeled shoes

Young females with mild hallux valgus (HV) have been identified as having an increased risk of first ray deformation. Little is known, however, about the biomechanical changes that might contribute to this increased risk. The purpose of this study was to compare kinetics changes during walking for mild HV subjects with high-heel-height shoes. Twelve female subjects (six with mild HV and six controls) participated in this study with heel height varying from 0 cm (barefoot) to 4.5 cm. Compared to healthy controls, patients had significantly higher peak pressure on the big toe area during barefoot walking. When the heel height increased, loading was transferred to medial side of the forefoot, and the big toe area suffered more impact compared to barefoot in mild HV. This study also demonstrated that the center of pressure (COP) inclines to medial side alteration after high-heeled shoes wearing. These findings indicate that mild HV people should be discouraged from wearing high-heeled shoes.