Chicken IL-6 is a heat-shock gene

The febrile response is elicited by pyrogenic cytokines including IL-6 in response to microorganism infections and diseases in vertebrates. Mammalian HSF1, which senses elevations in temperature, negatively regulates the response by suppressing pyrogenic cytokine expression. We here showed that HSF3, an avian ortholog of mammalian HSF1, directly binds to and activates IL-6 during heat shock in chicken cells. Other components of the febrile response mechanism, such as IL-1β and ATF3, were also differently regulated in mammalian and chicken cells. These results suggest that the febrile response is exacerbated by a feed-forward circuit composed of the HSF3-IL-6 pathway in birds.     

Intratumoral expression of IL-17 and its prognostic role in gastric adenocarcinoma patients

In this study, we characterized the intratumoral expression of IL-17 and CD8(+) TILs in gastric adenocarcinoma patients after resection and determined the correlation between the survival probability of gastric adenocarcinoma patients and the expression of IL-17 in tumor. Expression of IL-17 and CD8 was assessed by immunohistochemistry, and the prognostic effects of intratumoral IL-17 expression and CD8(+) TILs were evaluated by Cox regression and Kaplan-Meier analysis. Immunohistochemical detection revealed the presence of IL-17 and CD8(+) cells in gastric adenocarcinoma tissue samples (90.6%, 174 out of 192 patients and 96.9%, 186 out of 192 patients, respectively). We have also found that intratumoral IL-17 expression was significantly correlated with age (p=0.004) and that the number of CD8(+)TILs was significantly correlated with UICC staging (p=0.012) and the depth of tumor invasion (p=0.022). The five-year overall survival probability among patients intratumorally expressing higher levels of IL-17 was significantly better than those expressing lower levels of IL-17 (p=0.036). Multivariate Cox proportional hazard analyses revealed that intratumoral IL-17 expression (HR: 0.521; 95% CI: 0.329-0.823; p=0.005) was an independent factor affecting the five-year overall survival probability. We conclude that low levels of intratumoral IL-17 expression may indicate poor prognosis in gastric adenocarcinoma patients.     

Formation of soil organic carbon pool is regulated by the structure of dissolved organic matter and microbial carbon pump efficacy: A decadal study comparing different carbon management strategies

To achieve long-term increases in soil organic carbon (SOC) storage, it is essential to understand the effects of carbon management strategies on SOC formation pathways, particularly through changes in microbial necromass carbon (MNC) and dissolved organic carbon (DOC). Using a 14-year field study, we demonstrate that both biochar and maize straw lifted the SOC ceiling, but through different pathways. Biochar, while raising SOC and DOC content, decreased substrate degradability by increasing carbon aromaticity. This resulted in suppressed microbial abundance and enzyme activity, which lowered soil respiration, weakened in vivo turnover and ex vivo modification for MNC production (i.e., low microbial carbon pump “efficacy”), and led to lower efficiency in decomposing MNC, ultimately resulting in the net accumulation of SOC and MNC. In contrast, straw incorporation increased the content and decreased the aromaticity of SOC and DOC. The enhanced SOC degradability and soil nutrient content, such as total nitrogen and total phosphorous, stimulated the microbial population and activity, thereby boosting soil respiration and enhancing microbial carbon pump “efficacy” for MNC production. The total C added to biochar and straw plots were estimated as 27.3–54.5 and 41.4 Mg C ha⁻¹, respectively. Our results demonstrated that biochar was more efficient in lifting the SOC stock via exogenous stable carbon input and MNC stabilization, although the latter showed low “efficacy”. Meanwhile, straw incorporation significantly promoted net MNC accumulation but also stimulated SOC mineralization, resulting in a smaller increase in SOC content (by 50%) compared to biochar (by 53%–102%). The results address the decadal-scale effects of biochar and straw application on the formation of the stable organic carbon pool in soil, and understanding the causal mechanisms can allow field practices to maximize SOC content.     

Plasma metabonomics as a novel diagnostic approach for major depressive disorder

Major depressive disorder (MDD) is a socially detrimental psychiatric disorder, contributing to increased healthcare expenditures and suicide rates. However, no empirical laboratory-based tests are available to support the diagnosis of MDD. In this study, a NMR-based plasma metabonomic method for the diagnosis of MDD was tested. Proton nuclear magnetic resonance ((1)H NMR) spectra of plasma sampled from first-episode drug-na??ve depressed patients (n = 58) and healthy controls (n = 42) were recorded and analyzed by orthogonal partial least-squares discriminant analysis (OPLS-DA). The OPLS-DA score plots of the spectra demonstrated that the depressed patient group was significantly distinguishable from the healthy control group. Moreover, the method accurately diagnosed blinded samples (n = 26) in an independent replication cohort with a sensitivity and specificity of 92.8% and 83.3%, respectively. Taken together, NMR-based plasma metabonomics may offer an accurate empirical laboratory-based method applicable to the diagnosis of MDD.     

Evolutionary Analysis of Human Immunodeficiency Virus Type 1 Therapies Based on Conditionally Replicating Vectors

Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1) during long-term treatment are challenged by the evolution of anti-viral resistance mutants. Recent studies have shown that gene therapy approaches based on conditionally replicating vectors (CRVs) could have many advantages over anti-viral drugs and other approaches to therapy, potentially including the ability to circumvent the problem of evolved resistance. However, research to date has not explored the evolutionary consequences of long-term treatment of HIV-1 infections with conditionally replicating vectors. In this study, we analyze a computational model of the within-host co-evolutionary dynamics of HIV-1 and conditionally replicating vectors, using the recently proposed ‘therapeutic interfering particle’ as an example. The model keeps track of the stochastic process of viral mutation, and the deterministic population dynamics of T cells as well as different strains of CRV and HIV-1 particles. We show that early in the co-infection, mutant HIV-1 genotypes that escape suppression by CRV therapy appear; this is similar to the dynamics observed in drug treatments and other gene therapies. In contrast to other treatments, however, the CRV population is able to evolve and catch up with the dominant HIV-1 escape mutant and persist long-term in most cases. On evolutionary grounds, gene therapies based on CRVs appear to be a promising tool for long-term treatment of HIV-1. Our model allows us to propose design principles to optimize the efficacy of this class of gene therapies. In addition, because of the analogy between CRVs and naturally-occurring defective interfering particles, our results also shed light on the co-evolutionary dynamics of wild-type viruses and their defective interfering particles during natural infections.     

Pyrethroids as Promising Marine Antifoulants: Laboratory and Field Studies

Due to the regulations and bans regarding the use of traditional toxic chemicals against marine fouling organisms and the practical impediments to the commercialization of natural product antifoulants, there is an urgent need for compounds that are antifouling-active, environmentally friendly, and have a potential for commercial application. In this study, a series of common, commercially available pyrethroid products, which are generally used as environmentally safe insecticides, was evaluated for antifouling activity in the laboratory using an anti-settlement test with cyprids of the barnacle Balanus albicostatus and also in a field experiment. Laboratory assay showed that all eleven pyrethroids (namely, rich d-trans-allethrin, Es-biothrin, rich d-prallethrin, S-prallethrin, tetramethrin, rich d-tetramethrin, phenothrin, cyphenothrin, permethrin, cypermethrin, and high active cypermethrin) were able to inhibit barnacle settlement (EC₅₀ range of 0.0316 to 87.00 μg/ml) without significant toxicity. Analysis of structure–activity relationships suggested that the cyano group at the α-carbon position had a significant influence on the expression of antifouling activity in pyrethroids. In the field, the antifouling activity of pyrethroids was further confirmed, with the most potent pyrethroids being cypermethrin and high active cypermethrin, which displayed efficiency comparable with that of tributyltin. In summary, our investigation indicated that these pyrethroids have a great and practical commercial potential as antifouling agents.     

Direct and indirect effects of ski run management on alpine Orthoptera

Alpine landscapes are heavily influenced by ski run management, which can have severe impacts on alpine biodiversity. To assess these impacts on alpine Orthoptera, we compared species richness and species abundance in 41 plot pairs on ski runs and adjacent off-slope control plots in three ski resorts in Austria and Germany. A mixed modelling approach was used to assess the impacts of ski run preparation, artificial snow-making and environmental variables such as altitude, cover of dwarf shrubs and the application of fertilizer. Ski run plots showed a significantly lower species richness and number of individuals than control plots. Moreover, artificial snow led to a further decrease in species number. Hierarchical variance partitioning revealed that Orthoptera community composition is best predicted by environmental variables indirectly related to ski run management (fertilization, cover of dwarf shrubs) and to altitude. Only one out of five species significantly decreased in abundance after artificial snow-making. Other species were more sensitive to fertilizing and altitude. Dwarf shrubs were negatively associated with ski run management but positively associated with abundance of three species and species richness. Our data provide evidence for both direct and indirect consequences of ski runs and artificial snow-making on alpine Orthoptera. Overall, Orthoptera communities are suitable indicators for human-induced changes in alpine environments. In particular, a shift towards generalist species such as Chorthippus parallelus along with a decrease in typical alpine species gives cause for concern as this implies a homogenisation of biodiversity owing to ski run management.     

RBM10 inhibits cell proliferation of lung adenocarcinoma via RAP1/AKT/CREB signalling pathway

Initial functional studies have demonstrated that RNA‐binding motif protein 10 (RBM10) can promote apoptosis and suppress cell proliferation; however, the results of several studies suggest a tumour‐promoting role for RBM10. Herein, we assessed the involvement of RBM10 in lung adenocarcinoma cell proliferation and explored the potential molecular mechanism. We found that, both in vitro and in vivo, RBM10 overexpression suppresses lung adenocarcinoma cell proliferation, while its knockdown enhances cell proliferation. Using complementary DNA microarray analysis, we previously found that RBM10 overexpression induces significant down‐regulation of RAP1A expression. In this study, we have confirmed that RBM10 decreases the activation of RAP1 and found that EPAC stimulation and inhibition can abolish the effects of RBM10 knockdown and overexpression, respectively, and regulate cell growth. This effect of RBM10 on proliferation was independent of the MAPK/ERK and P38/MAPK signalling pathways. We found that RBM10 reduces the phosphorylation of CREB via the AKT signalling pathway, suggesting that RBM10 exhibits its effect on lung adenocarcinoma cell proliferation via the RAP1/AKT/CREB signalling pathway.