Increased graft-versus-host response of parental-strain (donor) lymphoid cells in cyclophosphamide-treated F1 recipients.

Cyclophosphamide (CY) treatment of F₁ hybrid mice increases their susceptibility to attack by parental-strain lymphoid cells. The donor cells may contribute to this increased susceptibility either by a more vigorous response to the host antigens, or by an increase in their colonization of the host's tissues. We have assessed the responsiveness of the donor cells in the CY-treated host through the use of a local graft-versus-host (GVH) assay. This assay is not influenced by changes in the capacity of donor cells to colonize host tissues, and thus colonization has been eliminated as a variable. In this assay donor lymph node tissue is grafted onto the cut surface of host kidney, and a local GVH reaction is indicated by enlargement of the donor tissue. We show that treatment of F₁ hosts with CY (100 mg/kg) 24 hr prior to grafting leads to increased responsiveness of the donor cells as measured by enlargement of the donor tissue.     

Virulence and pathogenicity of Candida albicans is enhanced in biofilms containing oral bacteria

This study examined the influence of bacteria on the virulence and pathogenicity of candidal biofilms. Mature biofilms (Candida albicans-only, bacteria-only, C. albicans with bacteria) were generated on acrylic and either analysed directly, or used to infect a reconstituted human oral epithelium (RHOE). Analyses included Candida hyphae enumeration and assessment of Candida virulence gene expression. Lactate dehydrogenase (LDH) activity and Candida tissue invasion following biofilm infection of the RHOE were also measured. Candida hyphae were more prevalent (p < 0.05) in acrylic biofilms also containing bacteria, with genes encoding secreted aspartyl-proteinases (SAP4/SAP6) and hyphal-wall protein (HWP1) up-regulated (p < 0.05). Candida adhesin genes (ALS3/EPA1), SAP6 and HWP1 were up-regulated in mixed-species biofilm infections of RHOE. Multi-species infections exhibited higher hyphal proportions (p < 0.05), up-regulation of IL-18, higher LDH activity and tissue invasion. As the presence of bacteria in acrylic biofilms promoted Candida virulence, consideration should be given to the bacterial component when managing denture biofilm associated candidoses.     

Evidence of an increased incidence of day 3 parasitaemia in Suriname: an indicator of the emerging resistance of Plasmodium falciparum to artemether

The emerging resistance to artemisinin derivatives that has been reported in South-East Asia led us to assess the efficacy of artemether-lumefantrine as the first line therapy for uncomplicated Plasmodium falciparum infections in Suriname. This drug assessment was performed according to the recommendations of the World Health Organization in 2011. The decreasing number of malaria cases in Suriname, which are currently limited to migrating populations and gold miners, precludes any conclusions on artemether efficacy because adequate numbers of patients with 28-day follow-up data are difficult to obtain. Therefore, a comparison of day 3 parasitaemia in a 2011 study and in a 2005/2006 study was used to detect the emergence of resistance to artemether. The prevalence of day 3 parasitaemia was assessed in a study in 2011 and was compared to that in a study in 2005/2006. The same protocol was used in both studies and artemether-lumefantrine was the study drug. Of 48 evaluable patients in 2011, 15 (31%) still had parasitaemia on day 3 compared to one (2%) out of 45 evaluable patients in 2005/2006. Overall, 11 evaluable patients in the 2011 study who were followed up until day 28 had negative slides and similar findings were obtained in all 38 evaluable patients in the 2005/2006 study. The significantly increased incidence of parasite persistence on day 3 may be an indication of emerging resistance to artemether.     

Soil carbon sequestration and land use change associated with biofuel production: empirical evidence

Soil organic carbon (SOC) change can be a major impact of land use change (LUC) associated with biofuel feedstock production. By collecting and analyzing data from worldwide field observations of major LUCs from cropland, grassland, and forest to lands producing biofuel crops (i.e. corn, switchgrass, Miscanthus, poplar, and willow), we were able to estimate SOC response ratios and sequestration rates and evaluate the effects of soil depth and time scale on SOC change. Both the amount and rate of SOC change were highly dependent on the specific land transition. Irrespective of soil depth or time horizon, cropland conversions resulted in an overall SOC gain of 6–14% relative to initial SOC level, while conversion from grassland or forest to corn (without residue removal) or poplar caused significant carbon loss (9–35%). No significant SOC changes were observed in land converted from grasslands or forests to switchgrass, Miscanthus, or willow. The SOC response ratios were similar in both 0–30 and 0–100 cm soil depths in most cases, suggesting SOC changes in deep soil and that use of top soil only for SOC accounting in biofuel life cycle analysis (LCA) might underestimate total SOC changes. Soil carbon sequestration rates varied greatly among studies and land transition types. Generally, the rates of SOC change tended to be the greatest during the 10 years following land conversion and had declined to approach 0 within about 20 years for most LUCs. Observed trends in SOC change were generally consistent with previous reports. Soil depth and duration of study significantly influence SOC change rates and so should be considered in carbon emission accounting in biofuel LCA. High uncertainty remains for many perennial systems and forest transitions, additional field trials, and modeling efforts are needed to draw conclusions about the site‐ and system‐specific rates and direction of change.     

A superposition free method for protein conformational ensemble analyses and local clustering based on a differential geometry representation of backbone

Here a differential geometry (DG) representation of protein backbone is explored on the analyses of protein conformational ensembles. The protein backbone is described by curvature, κ, and torsion, τ, values per residue and we propose 1) a new dissimilarity and protein flexibility measurement and 2) a local conformational clustering method. The methods were applied to Ubiquitin and c-Myb-KIX protein conformational ensembles and results show that κ\τ metric space allows to properly judge protein flexibility by avoiding the superposition problem. The d_max measurement presents equally good or superior results when compared to RMSF, especially for the intrinsically unstructured protein. The clustering method is unique as it relates protein global to local dynamics by providing a global clustering solutions per residue. The methods proposed can be especially useful to the analyses of highly flexible proteins. The software written for the analyses presented here is available at https://github.com/AMarinhoSN/FleXgeo for academic usage only.     

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO₃) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO₃ groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO₃ 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.     

Smoke Rings: Towards a Comprehensive Tobacco Free Policy for the Olympic Games

Background

The tobacco industry has long sought affiliation with major sporting events, including the Olympic Games, for marketing, advertising and promotion purposes. Since 1988, each Olympic Games has adopted a tobacco-free policy. Limited study of the effectiveness of the smoke-free policy has been undertaken to date, with none examining the tobacco industry’s involvement with the Olympics or use of the Olympic brand.

Methods and Findings

A comparison of the contents of Olympic tobacco-free policies from 1988 to 2014 was carried out by searching the websites of the IOC and host NOCs. The specific tobacco control measures adopted for each Games were compiled and compared with measures recommended by the WHO Tobacco Free Sports Initiative and Article 13 of the Framework Convention on Tobacco Control (FCTC). This was supported by semi-structured interviews of key informants involved with the adoption of tobacco-free policies for selected games. To understand the industry’s interests in the Olympics, the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) was systematically searched between June 2013 and August 2014. Company websites, secondary sources and media reports were also searched to triangulate the above data sources.This paper finds that, while most direct associations between tobacco and the Olympics have been prohibited since 1988, a variety of indirect associations undermine the Olympic tobacco-free policy. This is due to variation in the scope of tobacco-free policies, limited jurisdiction and continued efforts by the industry to be associated with Olympic ideals.

Conclusions

The paper concludes that, compatible with the IOC’s commitment to promoting healthy lifestyles, a comprehensive tobacco-free policy with standardized and binding measures should be adopted by the International Olympic Committee and all national Olympic committees.     

The M/GP5 Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner

The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus receptors and entry mediators. However, viral counterparts for these molecules have remained elusive and this has made rational development of new generation vaccines impossible. The main objective of this study was to identify the viral counterparts for sialoadhesin, a crucial PRRSV receptor on macrophages. For this purpose, a soluble form of sialoadhesin was constructed and validated. The soluble sialoadhesin could bind PRRSV in a sialic acid-dependent manner and could neutralize PRRSV infection of macrophages, thereby confirming the role of sialoadhesin as an essential PRRSV receptor on macrophages. Although sialic acids are present on the GP₃, GP₄ and GP₅ envelope glycoproteins, only the M/GP₅ glycoprotein complex of PRRSV was identified as a ligand for sialoadhesin. The interaction was found to be dependent on the sialic acid binding capacity of sialoadhesin and on the presence of sialic acids on GP₅. These findings not only contribute to a better understanding of PRRSV biology, but the knowledge and tools generated in this study also hold the key to the development of a new generation of PRRSV vaccines.