Nutrient flux and budget in the Ebro estuary

The Ebro river flows to the Mediterranean coast of Spain. During its final stretch, the Ebro behaves in a similar way to a highly stratified estuary. This paper describes the transport of nutrients to the Ebro estuary, evaluates the general movement of nutrients in the estuarine region, using a mass balance approach, and estimates the amounts of nutrients discharged to the coastal environment. Given the strong saline stratification, this study only includes the surface layer that contains the continental freshwater. The annual nutrient budget for the Ebro estuary shows a net excess for nitrogen and phosphorus, while silicate almost attains equilibrium between addition and removal. There are several reasons for gains in nitrogen and phosphorous: a contribution of dissolved and particulate compounds in the freshwater (some of which are mineralized); a lower uptake of phytoplankton indicated by chlorophyll reduction in the estuary; an entrainment of the nutrient-rich upper part of the salt wedge; and, to a lesser extent, the impact of wastewater and agricultural water use. The biggest load discharged into the Mediterranean Sea by the Ebro is nitrogen, followed by silicate with over 10 000 tons of each deposited annually. Phosphorus is discharged at relatively low concentrations and with an annual load of about 200 t yr¿1.This project was funded by the European Union in the framework of the MAST-III research project: "Preparation and Integration of Analysis Tools towards Operational Forecast of Nutrients in Estuaries of European Rivers (PIONEER)", Reference No. MAS3-CT98-0170.Falco Giaccaglia, SL.; Niencheski, L.; Rodilla Alamá, M.; Romero Gil, I.; González Del Rio Rams, J.; Sierra, J.; Mösso, C. (2010). Nutrient flux and budget in the Ebro estuary. Estuarine, Coastal and Shelf Science. 87(1):92-102. doi:10.1016/j.ecss.2009.12.020S9210287

Comparative effectiveness of autologous hematopoietic stem cell transplant vs fingolimod, natalizumab, and ocrelizumab in highly active relapsing-remitting multiple sclerosis

Importance: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). Objective: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. Design, Setting, and Participants: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. Exposure: AHSCT vs fingolimod, natalizumab, or ocrelizumab. Main outcomes: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. Results: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730 [49.0%]), AHSCT (146 [87.4%]) was associated with marginally lower ARR (mean [SD], 0.08 [0.31] vs 0.10 [0.34]), similar risk of disability worsening (HR, 1.06; 95% CI, 0.54-2.09), and higher chance of disability improvement (HR, 2.68; 95% CI, 1.72-4.18) over 5 years. AHSCT (110 [65.9%]) and ocrelizumab (343 [49.0%]) were associated with similar ARR (mean [SD], 0.09 [0.34] vs 0.06 [0.32]), disability worsening (HR, 1.77; 95% CI, 0.61-5.08), and disability improvement (HR, 1.37; 95% CI, 0.66-2.82) over 3 years. AHSCT-related mortality occurred in 1 of 159 patients (0.6%). Conclusion: In this study, the association of AHSCT with preventing relapses and facilitating recovery from disability was considerably superior to fingolimod and marginally superior to natalizumab. This study did not find evidence for difference in the effectiveness of AHSCT and ocrelizumab over a shorter available follow-up time

MicroRNA-155 Expression Is Enhanced by T-cell Receptor Stimulation Strength and Correlates with Improved Tumor Control in Melanoma.

microRNAs are short noncoding RNAs that regulate protein expression posttranscriptionally. We previously showed that miR-155 promotes effector CD8 <sup>+</sup> T-cell responses. However, little is known about the regulation of miR-155 expression. Here, we report that antigen affinity and dose determine miR-155 expression in CD8 <sup>+</sup> T cells. In B16 tumors expressing a low-affinity antigen ligand, tumor-specific infiltrating CD8 <sup>+</sup> T cells showed variable miR-155 expression, whereby high miR-155 expression was associated with more cytokine-producing cells and tumor control. Moreover, anti-PD-1 treatment led to both increased miR-155 expression and tumor control by specific CD8 <sup>+</sup> T cells. In addition, miR-155 overexpression enhanced exhausted CD8 <sup>+</sup> T-cell persistence in the LCMV cl13 chronic viral infection model. In agreement with these observations in mouse models, miR-155 expression in human effector memory CD8 <sup>+</sup> T cells positively correlated with their frequencies in tumor-infiltrated lymph nodes of melanoma patients. Low miR-155 target gene signature in tumors was associated with prolonged overall survival in melanoma patients. Altogether, these results raise the possibility that high miR-155 expression in CD8 <sup>+</sup> tumor-infiltrating T cells may be a surrogate marker of the relative potency of in situ antigen-specific CD8 <sup>+</sup> T-cell responses

Cnidarian gene expression patterns and the origins of bilaterality – are cnidarians reading the same game plan as "higher" animals?

[Extract] The past few years have seen a dramatic increase in the available data on gene sequence and gene expression for cnidarians and other "lower" Metazoa, and a flurry of recent papers has drawn on these to address the origins of bilaterality. Cnidarianhomologs of many genes that play key roles in the specification of both the A/P and D/V axes of bilaterians have been characterized, and their patterns of expression determined. Some of these expression patterns are consistent with the conservation of function between Cnidaria and Bilateria, but others clearly differ. Moreover, in some cases very different interpretations have been made on the basis of the same, or similar,\ud data. In part, these differences reflect the inevitable uncertainties associated with the depth of the divergence between cnidarians and bilaterians. In this paper we briefly summarize the cnidarian data on gene expression\ud and organization relevant to axis formation, the varying interpretations of these data, and where they conflict. Our conclusion is that the oral-aboral axis probably does correspond to the anterior-posterior axis of bilaterians,\ud but that its polarity remains uncertain, and that many of the same genes are involved in determining the directive axis of cnidarians and the dorsal-ventral axis of bilaterians, but with sufficient differences in expression that exact homologies are uncertain