Comparative analysis of the lambda-interferons IL-28A and IL-29 regarding their transcriptome and their antiviral properties against hepatitis C virus.

Specific differences in signaling and antiviral properties between the different Lambda-interferons, a novel group of interferons composed of IL-28A, IL-28B and IL-29, are currently unknown. This is the first study comparatively investigating the transcriptome and the antiviral properties of the Lambda-interferons IL-28A and IL-29. Expression studies were performed by microarray analysis, quantitative PCR (qPCR), reporter gene assays and immunoluminometric assays. Signaling was analyzed by Western blot. HCV replication was measured in Huh-7 cells expressing subgenomic HCV replicon. All hepatic cell lines investigated as well as primary hepatocytes expressed both IFN-λ receptor subunits IL-10R2 and IFN-λR1. Both, IL-28A and IL-29 activated STAT1 signaling. As revealed by microarray analysis, similar genes were induced by both cytokines in Huh-7 cells (IL-28A: 117 genes; IL-29: 111 genes), many of them playing a role in antiviral immunity. However, only IL-28A was able to significantly down-regulate gene expression (n = 272 down-regulated genes). Both cytokines significantly decreased HCV replication in Huh-7 cells. In comparison to liver biopsies of patients with non-viral liver disease, liver biopsies of patients with HCV showed significantly increased mRNA expression of IL-28A and IL-29. Moreover, IL-28A serum protein levels were elevated in HCV patients. In a murine model of viral hepatitis, IL-28 expression was significantly increased. IL-28A and IL-29 are up-regulated in HCV patients and are similarly effective in inducing antiviral genes and inhibiting HCV replication. In contrast to IL-29, IL-28A is a potent gene repressor. Both IFN-λs may have therapeutic potential in the treatment of chronic HCV

Amniotic fluid deficiency and congenital abnormalities both influence fluctuating asymmetry in developing limbs of human deceased fetuses

Fluctuating asymmetry (FA), as an indirect measure of developmental instability (DI), has been intensively studied for associations with stress and fitness. Patterns, however, appear heterogeneous and the underlying causes remain largely unknown. One aspect that has received relatively little attention in the literature is the consequence of direct mechanical effects on asymmetries. The crucial prerequisite for FA to reflect DI is that environmental conditions on both sides should be identical. This condition may be violated during early human development if amniotic fluid volume is deficient, as the resulting mechanical pressures may increase asymmetries. Indeed, we showed that limb bones of deceased human fetuses exhibited increased asymmetry, when there was not sufficient amniotic fluid (and, thus, space) in the uterine cavity. As amniotic fluid deficiency is known to cause substantial asymmetries and abnormal limb development, these subtle asymmetries are probably at least in part caused by the mechanical pressures. On the other hand, deficiencies in amniotic fluid volume are known to be associated with other congenital abnormalities that may disturb DI. More specifically, urogenital abnormalities can directly affect/reduce amniotic fluid volume. We disentangled the direct mechanical effects on FA from the indirect effects of urogenital abnormalities, the latter presumably representing DI. We discovered that both factors contributed significantly to the increase in FA. However, the direct mechanical effect of uterine pressure, albeit statistically significant, appeared less important than the effects of urogenital abnormalities, with an effect size only two-third as large. We, thus, conclude that correcting for the relevant direct factors allowed for a representative test of the association between DI and stress, and confirmed that fetuses form a suitable model system to increase our understanding in patterns of FA and symmetry development.Research Fund of the University of Antwerp, mobility grant from the Research Foundation – Flanders (FWO)

The clinical significance of incidental intra-abdominal findings on positron emission tomography performed to investigate pulmonary nodules

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a common cause of cancer-related death. Staging typically includes positron emission tomography (PET) scanning, in which¹⁸F-fluoro-2-dexoy-D-glucose (FDG) is taken up by cells proportional to metabolic activity, thus aiding in differentiating benign and malignant pulmonary nodules. Uptake of FDG can also occur in the abdomen. The clinical significance of incidental intraabdominal FDG uptake in the setting of pulmonary nodules is not well established. Our objective was to report on the clinical significance of incidental intra-abdominal FDG activity in the setting of lung cancer.</p> <p>Methods</p> <p>Fifteen hundred FDG-PET reports for studies performed for lung cancer were retrospectively reviewed for the presence of incidental FDG-positive intraabdominal findings. Patient charts with positive findings were then reviewed and information extracted.</p> <p>Results</p> <p>Twenty-five patients (25/1500) demonstrated incidental intraabdominal FDG uptake thought to be significant (1.7%) with a mean patient age of 71 years. Colonic uptake was most common (n = 17) with 9 (52%) being investigated further. Of these 9 cases, a diagnosis of malignancy was made in 3 patients, pre-malignant adenomas in 2 patients, a benign lipoma in 1 patient and no abnormal findings in the remaining patients. 8 patients were not investigated further (3 diagnosed with metastatic lung cancer and 2 were of advanced age) secondary to poor prognosis.</p> <p>Conclusion</p> <p>Incidental abdominal findings in the colon on FDG-PET scan for work-up of pulmonary nodules need to be further investigated by colonoscopy.</p

Adaptive Evolution of Cooperation through Darwinian Dynamics in Public Goods Games

The linear or threshold Public Goods game (PGG) is extensively accepted as a paradigmatic model to approach the evolution of cooperation in social dilemmas. Here we explore the significant effect of nonlinearity of the structures of public goods on the evolution of cooperation within the well-mixed population by adopting Darwinian dynamics, which simultaneously consider the evolution of populations and strategies on a continuous adaptive landscape, and extend the concept of evolutionarily stable strategy (ESS) as a coalition of strategies that is both convergent-stable and resistant to invasion. Results show (i) that in the linear PGG contributing nothing is an ESS, which contradicts experimental data, (ii) that in the threshold PGG contributing the threshold value is a fragile ESS, which cannot resist the invasion of contributing nothing, and (iii) that there exists a robust ESS of contributing more than half in the sigmoid PGG if the return rate is relatively high. This work reveals the significant effect of the nonlinearity of the structures of public goods on the evolution of cooperation, and suggests that, compared with the linear or threshold PGG, the sigmoid PGG might be a more proper model for the evolution of cooperation within the well-mixed population

Acanthaster planci Outbreak: Decline in Coral Health, Coral Size Structure Modification and Consequences for Obligate Decapod Assemblages

Although benthic motile invertebrate communities encompass the vast majority of coral reef diversity, their response to habitat modification has been poorly studied. A variety of benthic species, particularly decapods, provide benefits to their coral host enabling them to cope with environmental stressors, and as a result benefit the overall diversity of coral-associated species. However, little is known about how invertebrate assemblages associated with corals will be affected by global perturbations, (either directly or indirectly via their coral host) or their consequences for ecosystem resilience. Analysis of a ten year dataset reveals that the greatest perturbation at Moorea over this time was an outbreak of the corallivorous sea star Acanthaster planci from 2006 to 2009 impacting habitat health, availability and size structure of Pocillopora spp. populations and highlights a positive relationship between coral head size and survival. We then present the results of a mensurative study in 2009 conducted at the end of the perturbation (A. planci outbreak) describing how coral-decapod communities change with percent coral mortality for a selected coral species, Pocillopora eydouxi. The loss of coral tissue as a consequence of A. planci consumption led to an increase in rarefied total species diversity, but caused drastic modifications in community composition driven by a shift from coral obligate to non-obligate decapod species. Our study highlights that larger corals left with live tissue in 2009, formed a restricted habitat where coral obligate decapods, including mutualists, could subsist. We conclude that the size structure of Pocillopora populations at the time of an A. planci outbreak may greatly condition the magnitude of coral mortality as well as the persistence of local populations of obligate decapods

Particulate air pollution and survival in a COPD cohort

<p>Abstract</p> <p>Background</p> <p>Several studies have shown cross-sectional associations between long term exposure to particulate air pollution and survival in general population or convenience cohorts. Less is known about susceptibility, or year to year changes in exposure. We investigated whether particles were associated with survival in a cohort of persons with COPD in 34 US cities, eliminating the usual cross-sectional exposure and treating PM₁₀as a within city time varying exposure.</p> <p>Methods</p> <p>Using hospital discharge data, we constructed a cohort of persons discharged alive with chronic obstructive pulmonary disease using Medicare data between 1985 and 1999. 12-month averages of PM₁₀were merged to the individual annual follow up in each city. We applied Cox's proportional hazard regression model in each city, with adjustment for individual risk factors.</p> <p>Results</p> <p>We found significant associations in the survival analyses for single year and multiple lag exposures, with a hazard ratio for mortality for an increase of 10 μg/m³PM₁₀over the previous 4 years of 1.22 (95% CI: 1.17–1.27).</p> <p>Conclusion</p> <p>Persons discharged alive for COPD have substantial mortality risks associated with exposure to particles. The risk is evident for exposure in the previous year, and higher in a 4 year distributed lag model. These risks are significantly greater than seen in time series analyses.</p

Downbeat nystagmus, ataxia and spastic tetraparesis due to coeliac disease

A 25-year-old female presented to a university neurology clinic with a 1-month history of progressive ataxia, downbeat nystagmus and spastic tetraparesis. Personal history revealed polyarthralgias and weight loss. Family history was negative. Following thorough history, laboratory, neurophysiological and MRI investigations, a diagnosis of cerebellar ataxia due to coeliac disease was done. The patient was treated with strict gluten-free diet and intravenous administration of immunoglobulins. Although there are many controversies about neurological manifestations of coeliac disease, this case pointed to strong association between these two disorders. The findings of elevated protein content in the cerebrospinal fluid with positive oligoclonal bands suggested an immune-mediated process, further supported by positive anti-endomysium antibodies and anti-transglutaminase antibodies in the cerebrospinal fluid