Geochemical Dynamics and Nitrous Oxide Release from the Hyporheic Zone of Streams

The hyporheic zones of streams and rivers, consisting of the sediments beneath and immediately adjacent to the stream channel, are an important site of geochemical processing. Due to the difficulty of measuring these geochemical processes in the hyporheic zone in situ with meaningful spatial and temporal resolution, we conducted multiple column and large-scale flume experiments to model 1D and 2D hyporheic flow paths and observed important geochemical reactions, including the production and consumption of nitrous oxide (N2O). N2O is a significant greenhouse gas, but the controls on its emissions from streams are poorly constrained. We describe the controlling factors for hyporheic N2O production and release, and also describe spatial and temporal trends in other geochemical processes occurring the hyporheic zone, including those relevant to pollutant remediation. Based on the literature examining pathways for N2O production in soils and sediments, the current understanding of physical properties of the hyporheic zone, and the existing studies of N2O emissions from streams and rivers, it appears that production of N2O via denitrification (and other pathways) occurs predominantly in the hyporheic zone, though production associated with suspended sediments may be significant in larger rivers or streams with high turbidity. Overall, lotic N2O emissions increase with nitrate and ammonia concentrations, and tend to be highest in the late spring and summer and downstream of wastewater treatment plants. Observations and models combining hydromorphogical and chemical variables suggest that N2O emissions decrease downstream as sedimentary processes decrease relative to processes in the surface water. Downstream sites could have large N2O emissions, however, due to inputs of dissolved inorganic nitrogen. Observations from column and flume experiments suggest that N2O emission from stream sediments requires subsurface residence times (and microbially mediated reduction rates) be sufficiently long (and fast reacting) to produce N2O by nitrate reduction, but also sufficiently short (or slow reacting) to limit N2O conversion to nitrogen gas. We also confirm previous observations that elevated nitrate and declining organic carbon reactivity increase N2O production. These findings will aid in determining where and when streams will be a source of atmospheric N2O emissions. Based on measurements of additional geochemical species collected during these experiments, spatial and temporal trends reflect microbiological processes, changing redox conditions, dissolution, sorption and desorption. In general, microbial respiration causes dissolved oxygen to decrease with residence time in the hyporheic zone, leading to aerobic and anaerobic zones, nitrate reduction, and a decreasing pH gradient. Most other species concentrations increase with residence time. We propose that increases in Ca, Mg, Si, Ba, and Sr with residence time are primarily due to silicate dissolution, and increases in Fe, Mn, Co, and As with distance along flow lines are due to reductive dissolution of metal oxides and desorption in the anoxic zone. Trends over elapsed time suggest higher flow velocities (as induced by steeper bedform dune morphologies) lead to more rapid consumption of reactive carbon, larger oxic zones, and decreases in most species over elapsed time. This description of the trends of chemical species will inform future studies into the many geochemical functions of the hyporheic zone

A Crosslinguistic Study of Child Code-Switching within the Noun Phrase: A Usage-Based Perspective

This paper aims to investigate whether language use can account for the differences in code-switching within the article-noun phrase in children exposed to English and German, French and Russian, and English and Polish. It investigates two aspects of language use: equivalence and segmentation. Four children’s speech is derived from corpora of naturalistic interactions recorded between the ages of two and three and used as a source of the children’s article-noun phrases. We demonstrate that children’s CS cannot be fully explained by structural equivalence in each two languages: there is CS in French-Russian although French does, and Russian does not, use articles. We also demonstrate that language pairs which use higher numbers of articles types, and therefore have more segmented article-noun phrases, are also more open to switching. Lastly, we show that longitudinal use of monolingual articles-noun phrases corresponds with the trends in the use of bilingual article-noun phrases. The German-English child only starts to mix English articles once they become more established in monolingual combinations while the French-Russian child ceases to mix French proto-articles with Russian nouns once target articles enter frequent use. These findings are discussed in the context of other studies which report code-switching across different language pairs

Left ventricular clefts - incidental finding or pathologic sign of Wilson's disease?

Background: Wilson’s disease is an inherited autosomal recessive multi-systemic disorder characterized by reduced excretion and consequently excessive accumulation of copper in different organs, such as the heart. Results: In a prospective controlled trial, which is the largest to date, we evaluated 61 patients with Wilson’s disease, age- and sex-matched to 61 healthy patients, for cardiac manifestation using cardiac magnetic resonance imaging. Patients were under stable disease and had no signs of heart failure at the time of examination. We detected a left ventricular cleft, an invagination penetrating more than 50% wall thickness of the adjoining compact myocardium in diastole, in 20% of the patients (12 out of 61) compared to 5% among control patients (3 out of 61, p = 0.013). No correlation between the incidence of cleft and a certain genotype of Wilson’s disease was found. All described cases were incidental findings and none of the patients showed other signs of cardiac involvement. Conclusions: To conclude, the results of this study suggests that the increased occurrence of left ventricular clefts is due to Wilson’s disease. Large studies with a long observation period are needed for further evaluation

Genomic mapping of Suppressor of Hairy-wing binding sites in Drosophila.

BACKGROUND: Insulator elements are proposed to play a key role in the organization of the regulatory architecture of the genome. In Drosophila, one of the best studied is the gypsy retrotransposon insulator, which is bound by the Suppressor of Hairy-wing (Su [Hw]) transcriptional regulator. Immunolocalization studies suggest that there are several hundred Su(Hw) sites in the genome, but few of these endogenous Su(Hw) binding sites have been identified. RESULTS: We used chromatin immunopurification with genomic microarray analysis to identify in vivo Su(Hw) binding sites across the 3 megabase Adh region. We find 60 sites, and these enabled the construction of a robust new Su(Hw) binding site consensus. In contrast to the gypsy insulator, which contains tightly clustered Su(Hw) binding sites, endogenous sites generally occur as isolated sites. These endogenous sites have three key features. In contrast to most analyses of DNA-binding protein specificity, we find that strong matches to the binding consensus are good predictors of binding site occupancy. Examination of occupancy in different tissues and developmental stages reveals that most Su(Hw) sites, if not all, are constitutively occupied, and these isolated Su(Hw) sites are generally highly conserved. Analysis of transcript levels in su(Hw) mutants indicate widespread and general changes in gene expression. Importantly, the vast majority of genes with altered expression are not associated with clustering of Su(Hw) binding sites, emphasizing the functional relevance of isolated sites. CONCLUSION: Taken together, our in vivo binding and gene expression data support a role for the Su(Hw) protein in maintaining a constant genomic architecture

Complexity and Community Context: Learning from the Evaluation Design of a National Community Empowerment Programme

Community empowerment interventions, which aim to build greater individual and community control over health, are shaped by the community systems in which they are implemented. Drawing on complex systems thinking in public health research, this paper discusses the evaluation approach used for a UK community empowerment programme focused on disadvantaged neighbourhoods. It explores design choices and the tension between the overall enquiry questions, which were based on a programme theory of change, and the varied dynamic socio-cultural contexts in intervention communities. The paper concludes that the complexity of community systems needs to be accounted for through in-depth case studies that incorporate community perspectives

Antioxidants can inhibit basal autophagy and enhance neurodegeneration in models of polyglutamine disease.

Many neurodegenerative diseases exhibit protein accumulation and increased oxidative stress. Therapeutic strategies include clearing aggregate-prone proteins by enhancing autophagy or decreasing oxidative stress with antioxidants. Many autophagy-inducing stimuli increase reactive oxygen species (ROS), raising concerns that the benefits of autophagy up-regulation may be counterbalanced by ROS toxicity. Here we show that not all autophagy inducers significantly increase ROS. However, many antioxidants inhibit both basal and induced autophagy. By blocking autophagy, antioxidant drugs can increase the levels of aggregate-prone proteins associated with neurodegenerative disease. In fly and zebrafish models of Huntington's disease, antioxidants exacerbate the disease phenotype and abrogate the rescue seen with autophagy-inducing agents. Thus, the potential benefits in neurodegenerative diseases of some classes of antioxidants may be compromised by their autophagy-blocking properties

Sex practices and awareness of Ebola virus disease among male survivors and their partners in Guinea.

INTRODUCTION: Towards the end of the 2013-2016 West African outbreak, sexually-transmitted Ebola virus re-emerged from Ebola virus disease (EVD) survivors in all three hardest hit countries. We explore sex practices and awareness of the risk of Ebola virus transmission among EVD survivors and their partners. METHODS: In this cross-sectional study, we recruited a convenience sample of study participants aged >15 years who were male EVD survivors, their sexual partners and a comparison group. We administered a questionnaire to all respondents, estimated self-reported sexual practices and risk awareness and conducted in-depth interviews. RESULTS: We recruited 234 EVD survivors, 256 sexual partners of survivors and 65 individuals in the comparison group from five prefectures in Guinea. The prevalence of safe sexual behaviour (regular condom use or sexual abstinence >12 months) and regular condom use in EVD survivors was 38% (95% CI 31% to 44%) and 21% (95% CI 16% to 27%), respectively. Among partners, these prevalences were lower (11%, 95% CI 7% to 15% and 9%, 95% CI 5% to 12%, respectively). EVD survivors were more than five times as likely to engage in safe sexual behaviour compared with the comparison group (aOR 5.59, 95% CI 2.36 to 13.2). One-hundred and thirty one EVD survivors (57%) and 94 partners (37%) were aware of the risk of Ebola virus re-emergence associated with having unsafe sex. Partners who reported not being informed by their husband/boyfriend (EVD survivor) were more likely to be unaware of this risk (aOR 20.5, 95% CI 8.92 to 47.4). CONCLUSIONS: We disclose here a need to improve knowledge of the disease and close the gap between knowledge and practice found in EVD survivors and their partners. Current and future survivors' follow-up programmes should include partners and be more effective at communicating sex-related risks. Community-level fears and attitudes that enable stigmatisation should be addressed. Safe sex interventions targeting EVD survivors and their partners should be prioritised

Primitive layered gabbros from fast-spreading lower oceanic crust

Three-quarters of the oceanic crust formed at fast-spreading ridges is composed of plutonic rocks whose mineral assemblages, textures and compositions record the history of melt transport and crystallization between the mantle and the sea floor. Despite the importance of these rocks, sampling them in situ is extremely challenging owing to the overlying dykes and lavas. This means that models for understanding the formation of the lower crust are based largely on geophysical studies and ancient analogues (ophiolites) that did not form at typical mid-ocean ridges. Here we describe cored intervals of primitive, modally layered gabbroic rocks from the lower plutonic crust formed at a fast-spreading ridge, sampled by the Integrated Ocean Drilling Program at the Hess Deep rift. Centimetre-scale, modally layered rocks, some of which have a strong layering-parallel foliation, confirm a long-held belief that such rocks are a key constituent of the lower oceanic crust formed at fast-spreading ridges. Geochemical analysis of these primitive lower plutonic rocks-in combination with previous geochemical data for shallow-level plutonic rocks, sheeted dykes and lavas-provides the most completely constrained estimate of the bulk composition of fast-spreading oceanic crust so far. Simple crystallization models using this bulk crustal composition as the parental melt accurately predict the bulk composition of both the lavas and the plutonic rocks. However, the recovered plutonic rocks show early crystallization of orthopyroxene, which is not predicted by current models of melt extraction from the mantle and mid-ocean-ridge basalt differentiation. The simplest explanation of this observation is that compositionally diverse melts are extracted from the mantle and partly crystallize before mixing to produce the more homogeneous magmas that erupt

International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats:The REVEAL Study

Background: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. Hypothesis/Objectives: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). Animals: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). Methods: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. Results: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean \ub1 standard deviation, 1.3 \ub1 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. Conclusions and Clinical Importance: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival