Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.

The risk for non-Hodgkin lymphoma (NHL) is markedly increased in persons living with human immunodeficiency virus (HIV) infection, and remains elevated in those on anti-retroviral therapy (cART). Both the loss of immunoregulation of Epstein-Barr virus (EBV) infected cells, as well as chronic B-cell activation, are believed to contribute to the genesis of AIDS-related NHL (AIDS-NHL). However, the mechanisms that lead to AIDS-NHL have not been completely defined. A subset of B cells that is characterized by the secretion of IL10, as well as the expression of the programmed cell death ligand-1 (PD-L1/CD274), was recently described. These PD-L1+ B cells can exert regulatory function, including the dampening of T-cell activation, by interacting with the program cell death protein (PD1) on target cells. The role of PD-L1+ B cells in the development of AIDS-NHL has not been explored. We assessed B cell PD-L1 expression on B cells preceding AIDS-NHL diagnosis in a nested case-control study of HIV+ subjects who went on to develop AIDS-NHL, as well as HIV+ subjects who did not, using multi-color flow cytometry. Archival frozen viable PBMC were obtained from the UCLA Multicenter AIDS Cohort Study (MACS). It was seen that the number of CD19+CD24++CD38++and CD19+PD-L1+cells was significantly elevated in cases 1-4 years prior to AIDS-NHL diagnosis, compared to controls, raising the possibility that these cells may play a role in the etiology of AIDS-NHL. Interestingly, most PD-L1+ expression on CD19+ cells was seen on CD19+CD24++CD38++ cells. In addition, we showed that HIV can directly induce PD-L1 expression on B cells through interaction of virion-associated CD40L with CD40 on B cells

Author Correction: Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

BRAZILIAN FOREIGN VULNERABILITY IN THE 1980S: AN ANALYSIS OF THE INTERNATIONAL INVESTMENT POSITION AND INCOME FLOWS

O objetivo do trabalho é apresentar a vulnerabilidade externa brasileira na década de 1980, em sua esfera financeira, decorrente dos estoques externos. Defende-se a hipótese de que, historicamente, um dos elos mais importantes da interação entre os fluxos e os estoques externos brasileiros está na sua circularidade. Para as análises em tela, realiza-se uma estimativa da Posição Internacional de Investimentos para os anos 1980 que é inédita – já que esses dados não são disponibilizados por nenhuma fonte oficial –, constituindo-se como uma das contribuições do artigo. Ademais, apresenta-se uma estimativa – também inédita – da rentabilidade desses estoques externos, além de alguns indicadores de endividamento externo. A partir desses dados, o artigo analisa o período marcado pela crise da dívida externa no Brasil, concluindo que os saldos positivos gerados pelas exportações serviram apenas para amenizar a circularidade entre a Posição Internacional de Investimentos e as rendas enviadas, atenuando o aumento do passivo externo líquido ao longo do período analisado e gerando, em contrapartida, um baixo dinamismo econômico e o aumento das pressões inflacionárias.The objective of this paper is to present the Brazilian external vulnerability in the 1980s, in the financial sphere, resulting from foreign stocks. The paper supports the hypothesis that, historically, one of the most important links of the interaction between flows and external stocks in Brazil is in its circularity. In order to enable these analyses, the paper makes an estimation of the Brazilian International Investment Position in 1980 that is original and novel – since there are no official data for it –, what is certainly one of the contributions of this article. Moreover, it presents an estimation – also original – for the yield of these foreign stocks and some external debt indicators. Using these data, the paper analyzes the period marked by the Brazilian debt crisis in the 1980s, concluding that the surpluses generated by exports only served to soften the circularity between the International Investment Position and sent rents, reducing the increase in net foreign liabilities over the period, but generating a low economic dynamism and increasing inflationary pressures.

The proinflammatory cytokine interleukin 18 regulates feeding by acting on the bed nucleus of the stria terminalis

The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18R\u3b1 (Il18ra-/-), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons

The MEDESS-GIB database: tracking the Atlantic water inflow

García Sotillo, Marcos ... et al.-- 9 pages, 5 figures, 2 tablesOn 9 September 2014, an intensive drifter deployment was carried out in the Strait of Gibraltar. In the frame of the MEDESS-4MS Project (EU MED Program), the MEDESS-GIB experiment consisted of the deployment of 35 satellite tracked drifters, mostly of CODE-type, equipped with temperature sensor sampling at a rate of 30 min. Drifters were distributed along and on both sides of the Strait of Gibraltar. The MEDESS-GIB deployment plan was designed as to ensure quasi-synoptic spatial coverage. To this end, four boats covering an area of about 680NM2 in 6 h were coordinated. As far as these authors know, this experiment is the most important exercise in the area in terms of number of drifters released. Collected satellite-tracked data along drifter trajectories have been quality controlled and processed to build the presented MEDESS-GIB database. This paper reports the MEDESS-GIB data set that comprises drifter trajectories, derived surface currents and in situ SST measurements collected along the buoys tracks. This series of data is available through the PANGAEA (Data Publisher for Earth and Environmental Science) repository, with the following doi:10.1594/PANGAEA.853701. Likewise, the MEDESS-GIB data will be incorporated as part of the Copernicus Marine historical products. The MEDESS-GIB data set provides a complete Lagrangian view of the surface inflow of Atlantic waters through the Strait of Gibraltar and thus, very useful data for further studies on the surface circulation patterns in the Alboran Sea, and their links with one of the most energetic Mediterranean Sea flows: the Algerian CurrentThe MEDESS-GIB experiment was performed as part of the MEDESS-4MS Project activities (Project ref. 2S-MED11-01), supported by the European Regional Development Fund in the framework of the MED Programme. D. Conti is currently a PhD fellowship (FPI/1543/2013) granted by the Conselleria d’Educació, Cultura i Universitats from the Government of the Balearic Islands co-financed by the European Social Fund. J. M. Sayol is thankful for the financial support of CSIC and FSE with the JAE-pre PhD scholarship programPeer Reviewe

Effect of the anode composition on the performance of reversible chlor-alkali electro-absorption cells

In this work, the performances of a reversible electrochemical cell for the storage of energy using the chloralkaline process was investigated. The cell operates at room temperature with liquid electrolytes in both compartments. In the electrolyzer mode, the cell transforms a sodium chloride solution into hydrogen and chlorine, which is then disproportionated to form hypochlorous acid and hypochlorite. In fuel cell operation mode, the cell becomes an electro-absorber to oxidize hydrogen at the anode while reducing hypochlorous acid at the cathode. Because of the low solubility of hydrogen, a special mechanical device is used to produce hydrogen microbubbles in the anodic compartment. The influence of the ratio Ru/Pt in the electrode devoted to the electrochemistry of chlorine species is also evaluated. It was found that a molar ratio Ru:Pt in the range 3–4 was good enough to obtain a good performance in both operation modes (electrolyzer and fuel cell). In the electrode in charge of the hydrogen electrochemistry a platinum coating on Ti was used and it demonstrates robustness enough to obtain good operation results. Maximum efficiency in the electrolysis mode was 8.0 mmol H2/Wh while in the fuel cell mode, the maximum energy production reached 0.5 Wh/mol H2

Do Circulating Extracellular Vesicles Strictly Reflect Bronchoalveolar Lavage Extracellular Vesicles in COPD?

Cell-derived extracellular vesicles (EVs) found in the circulation and body fluids contain biomolecules that could be used as biomarkers for lung and other diseases. EVs from bronchoalveolar lavage (BAL) might be more informative of lung abnormalities than EVs from blood, where informa- tion might be diluted. To compare EVs’ characteristics in BAL and blood in smokers with and without COPD. Same-day BAL and blood samples were obtained in 9 nonsmokers (NS), 11 smokers w/o COPD (S), and 9 with COPD (SCOPD) (FEV1: 59 ± 3% pred). After differential centrifugation, EVs (200–500 nm diameter) were identified by flow cytometry and labeled with cell-type specific antigens: CD14 for macrophage-derived EVs, CD326 for epithelial-derived EVs, CD146 for endothelial-derived EVs, and CD62E for activated-endothelial-derived EVs. In BAL, CD14-EVs were increased in S compared to NS [384 (56–567) vs. 172 (115–282) events/μL; p = 0.007] and further increased in SCOPD [619 (224–888)] compared to both S (p = 0.04) and NS (p < 0.001). CD326-EVs were increased in S [760 (48–2856) events/μL, p < 0.001] and in SCOPD [1055 (194–11,491), p < 0.001] when compared to NS [15 (0–68)]. CD146-EVs and CD62E-EVs were similar in the three groups. In BAL, significant differences in macrophage and epithelial-derived EVs can be clearly detected between NS, S and SCOPD, while these differences were not found in plasma. This suggests that BAL is a better medium than blood to study EVs in lung diseases

Assessing the Malignant Ventricular Arrhythmic Substrate in Patients With Brugada Syndrome.

Background: Guidelines recommend the use of implanted cardioverter-defibrillators in patients with Brugada syndrome and induced ventricular tachyarrhythmias, but there is no evidence supporting it. Objectives: This prospective registry study was designed to explore clinical and electrophysiological predictors of malignant ventricular tachyarrhythmia inducibility in Brugada syndrome. Methods: A total of 191 consecutive selected patients with (group 1; n = 88) and without (group 2; n = 103) Brugada syndrome–related symptoms were prospectively enrolled in the registry. Patients underwent electrophysiological study and substrate mapping or ablation before and after ajmaline testing (1 mg/kg/5 min). Results: Overall, before ajmaline testing, 53.4% of patients had ventricular tachyarrhythmia inducibility, which was more frequent in group 1 (65.9%) than in group 2 (42.7%; p < 0.001). Regardless of clinical presentation, larger substrates with more fragmented long-duration ventricular potentials were found in patients with inducible arrhythmias than in patients without inducible arrhythmias (p < 0.001). One extrastimulus was used in more extensive substrates (median 13 cm2; p < 0.001), and ventricular fibrillation was the more frequently induced rhythm (p < 0.001). After ajmaline, patients without arrhythmia inducibility had arrhythmia inducibility without a difference in substrate characteristics between the 2 groups. The substrate size was the only independent predictor of inducibility (odds ratio: 4.51; 95% confidence interval: 2.51 to 8.09; p < 0.001). A substrate size of 4 cm2 best identified patients with inducible arrhythmias (area under the curve: 0.98; p < 0.001). Substrate ablation prevented ventricular tachyarrhythmia reinducibility. Conclusions: In Brugada syndrome dynamic substrate variability represents the pathophysiological basis of lethal ventricular tachyarrhythmias. Substrate size is independently associated with arrhythmia inducibility, and its determination after ajmaline identifies high-risk patients missed by clinical criteria. Substrate ablation is associated with electrocardiogram normalization and not arrhythmia reinducibility. (Epicardial Ablation in Brugada Syndrome [BRUGADA_I]; NCT02641431; Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701

Extracellular Vesicles in Pulmonary Hypertension: A Dangerous Liaison?

The term pulmonary hypertension (PH) refers to different conditions, all characterized by increased pressure and resistance in the pulmonary arterial bed. PH has a wide range of causes (essentially, cardiovascular, pulmonary, or connective tissue disorders); however, idiopathic (i.e., without a clear cause) PH exists. This chronic, progressive, and sometimes devastating disease can finally lead to right heart failure and eventually death, through pulmonary vascular remodeling and dysfunction. The exact nature of PH pathophysiology is sometimes still unclear. Extracellular vesicles (EVs), previously known as apoptotic bodies, microvesicles, and exosomes, are small membrane-bound vesicles that are generated by almost all cell types and can be detected in a variety of physiological fluids. EVs are involved in intercellular communication, thus influencing immunological response, inflammation, embryogenesis, aging, and regenerative processes. Indeed, they transport chemokines, cytokines, lipids, RNA and miRNA, and other biologically active molecules. Although the precise functions of EVs are still not fully known, there is mounting evidence that they can play a significant role in the pathophysiology of PH. In this review, after briefly recapping the key stages of PH pathogenesis, we discuss the current evidence on the functions of EVs both as PH biomarkers and potential participants in the distinct pathways of disease progression