The axis IL-10/claudin-10 is implicated in the modulation of aggressiveness of melanoma cells by B-1 lymphocytes

B-1 lymphocytes are known to increase the metastatic potential of B16F10 melanoma cells via the extracellular signal-regulated kinase (ERK) pathway. Since IL-10 is associated with B-1 cells performance, we hypothesized that IL-10 could be implicated in the progression of melanoma. In the present work, we found that the C57BL/6 mice, inoculated with B16F10 cells that were co-cultivated with B-1 lymphocytes from IL-10 knockout mice, developed fewer metastatic nodules than the ones which were injected with the melanoma cells that were cultivated in the presence of wild-type B-1 cells. The impairment of metastatic potential of the B16F10 cells was correlated with low activation of the ERK signaling pathway, supporting the idea that the production of IL-10 by B-1 cells influences the behavior of the tumor. A microarray analysis of the B-1 lymphocytes revealed that IL-10 deficiency is associated with down-regulation of the genes that code for claudin-10, a protein that is involved in cell-to-cell contact and that has been linked to lung adenocarcinoma. In order to determine the impact of claudin-10 in the cross-talk between B-1 lymphocytes and the B16F10 tumor cells, we took advantage of small interfering RNA. The silencing of claudin-10 gene in B-1 lymphocytes inhibited activation of the ERK pathway and abrogated the B-1-induced aggressive behavior of the B16F10 cells. Thus, our findings suggest that the axis IL-10/claudin-10 is a promising target for the development of therapeutic agents against aggressive melanoma.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Univ Paulista, Environm & Expt Pathol Program, Sao Paulo, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Diadema, SP, BrazilCtr Univ Sao Camilo, Sao Paulo, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Nephrol Div, Dept Med, Sao Paulo, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Pharmaceut Sci, Campus Diadema, Diadema, SP, BrazilUniv Fed Sao Paulo Escola Paulista Med UNIFESP EPM, Nephrol Div, Dept Med, Sao Paulo, SP, BrazilFAPESP: 11/50256-6FAPESP: 08/50632-5FAPESP: 2016/02189-1CNPq: 472035/2011-8CNPq: 308374/2016-9Web of Scienc

The BINGO project: VII. Cosmological forecasts from 21 cm intensity mapping

Context. The 21 cm line of neutral hydrogen (HI) opens a new avenue in our exploration of the structure and evolution of the Universe. It provides complementary data to the current large-scale structure (LSS) observations with different systematics, and thus it will be used to improve our understanding of the Icold dark matter (ICDM) model. This will ultimately constrain our cosmological models, attack unresolved tensions, and test our cosmological paradigm. Among several radio cosmological surveys designed to measure this line, BINGO is a single-dish telescope mainly designed to detect baryon acoustic oscillations (BAOs) at low redshifts (0.127 < z < 0.449). Aims. Our goal is to assess the fiducial BINGO setup and its capabilities of constraining the cosmological parameters, and to analyze the effect of different instrument configurations. Methods. We used the 21 cm angular power spectra to extract cosmological information about the HI signal and the Fisher matrix formalism to study BINGO's projected constraining power. Results. We used the Phase 1 fiducial configuration of the BINGO telescope to perform our cosmological forecasts. In addition, we investigated the impact of several instrumental setups, taking into account some instrumental systematics, and different cosmological models. Combining BINGO with Planck temperature and polarization data, the projected constraint improves from a 13% and 25% precision measurement at the 68% confidence level with Planck only to 1% and 3% for the Hubble constant and the dark energy (DE) equation of state (EoS), respectively, within the wCDM model. Assuming a Chevallier- Polarski- Linder (CPL) parameterization, the EoS parameters have standard deviations given by w0 = 0.30 and wa = 1.2, which are improvements on the order of 30% with respect to Planck alone. We also compared BINGO's fiducial forecast with future SKA measurements and found that, although it will not provide competitive constraints on the DE EoS, significant information about HI distribution can be acquired. We can access information about the HI density and bias, obtaining 8.5% and 6% precision, respectively, assuming they vary with redshift at three independent bins. BINGO can also help constrain alternative models, such as interacting dark energy and modified gravity models, improving the cosmological constraints significantly. Conclusions. The fiducial BINGO configuration will be able to extract significant cosmological information from the HI distribution and provide constraints competitive with current and future cosmological surveys. It will also help in understanding the HI physics and systematic effects

The BINGO project: IV. Simulations for mission performance assessment and preliminary component separation steps

Aims. The large-scale distribution of neutral hydrogen (HI) in the Universe is luminous through its 21 cm emission. The goal of the Baryon Acoustic Oscillations from Integrated Neutral Gas Observations (BINGO) radio telescope is to detect baryon acoustic oscillations at radio frequencies through 21 cm intensity mapping (IM). The telescope will span the redshift range 0.127<z<0.449 with an instantaneous field-of-view of 14.75 - 6.0. Methods. In this work we investigate different constructive and operational scenarios of the instrument by generating sky maps as they would be produced by the instrument. In doing this we use a set of end-to-end IM mission simulations. The maps will additionally be used to evaluate the efficiency of a component separation method (GNILC). Results. We have simulated the kind of data that would be produced in a single-dish IM experiment such as BINGO. According to the results obtained, we have optimized the focal plane design of the telescope. In addition, the application of the GNILC method on simulated data shows that it is feasible to extract the cosmological signal across a wide range of multipoles and redshifts. The results are comparable with the standard principal component analysis method

The BINGO Project: III. Optical design and optimization of the focal plane

Context. The Baryon Acoustic Oscillations from Integrated Neutral Gas Observations (BINGO) telescope was designed to measure the fluctuations of the 21 cm radiation arising from the hyperfine transition of neutral hydrogen. It is also aimed at measuring the baryon acoustic oscillations (BAO) from such fluctuations, thereby serving as a pathfinder to future, deeper intensity mapping surveys. The requirements for the Phase 1 of the projects consider a large reflector system (two 40 m-class dishes in a crossed-Dragone configuration) illuminating a focal plane with 28 horns to measure the sky, with two circular polarizations in a drift scan mode to produce measurements of the radiation in intensity (I) as well as the circular (V) polarization. Aims. In this paper, we present the optical design for the instrument. We describe the optical arrangement of the horns in the focal plane to produce a homogeneous and well-sampled map after the end of Phase 1, as well as the intensity and polarization properties of the beams. Our analysis provides an optimal model for the location of the horns in the focal plane, producing a homogeneous and Nyquist-sampled map after the nominal survey time. Methods. We used the GRASP package to model the focal plane arrangement and performed several optimization tasks to arrive at the current configuration, including an estimation of the sidelobes corresponding to the diffraction patterns of the two mirrors. The final model for the focal plane was defined through a combination of neural network and other direct optimization methods. Results. We arrived at an optimal configuration for the optical system that includes the focal plane positioning and the beam behavior of the instrument. We present an estimate of the expected sidelobes both for intensity and polarization, as well as the effect of band averaging on the final sidelobes, as well as an estimation of the cross-polarization leakage for the final configuration. Conclusions. We conclude that the chosen optical design meets the requirements for the project in terms of polarization purity and area coverage as well as a homogeneity of coverage so that BINGO can perform a successful BAO experiment. We further conclude that the requirements on the placement and rms error on the mirrors are also achievable so that a successful experiment can be conducted

Pediatric Patients With Steroid-Sensitive Nephrotic Syndrome Have Higher Expression of T Regulatory Lymphocytes in Comparison to Steroid-Resistant Disease

Background and Aim: Idiopathic nephrotic syndrome (INS) is classified according to the response to drug therapy in steroid-sensitive (SS), steroid-dependent (SD), and steroid-resistant (SR) categories. Previous studies showed changes in inflammatory activity of subpopulations of lymphocytes in INS. This study aimed to compare SS and SR patients in regard to subpopulations of leukocytes, profile of regulatory lymphocytes, and migratory activity of lymphocyte subpopulations. Results obtained in INS patients were also compared to age and sex-matched healthy controls.Methods: This is a cross-sectional study including SS patients (n = 30), SR patients (n = 14), and controls (n = 10). Peripheral blood samples were withdrawn for ex-vivo leukocyte flow cytometry analysis.Results: Percentage of B-lymphocytes and natural killer (NK) cells were significantly reduced in SR patients when compared to controls, while the percentage of NKT cells were decreased in SS patients in comparison to controls. Percentages of CD4+ expressing FoxP3 and CTLA4 were significantly higher in SS patients in comparison to SR patients and controls. The expression of integrin CD18 on the surface of T lymphocytes (CD3+) was reduced in SS patients if compared to controls.Conclusion: This study found that SS INS patients have higher levels of regulatory T-lymphocytes and lower expression of adhesion molecules than SR patients

Manobra de Kristeller: uma violência obstétrica / Kristeller’s maneuver: obstetric violence

Introdução: A violência obstétrica é desde abusos verbais, restringir a presença de acompanhante, procedimentos médicos não consentidos, violação de privacidade, recusa em administrar analgésicos, violência física, entre outros. Dessa forma, o termo “violência obstétrica” tornou-se um tema, de diferentes interpretações, que relata o sofrimento sentido, de diversas formas. Objetivo: Descrever a violência obstétrica através do uso da manobra de Kristeller em trabalhos publicados no Brasil nos últimos dez anos. Método: Trata-se de um estudo descritivo, com abordagem qualitativa, que utilizará um método de Revisão Integrativa da Literatura, nas plataformas SciElo, Lilacs e Pubmed em artigos publicados de 2010 a 2020. Resultados: Foram encontrados 259 artigos publicados sobre a temática, utilizando os descritores “Violência” e “Obstétrica”, e o operador booleano “AND”, sendo 89 da SciElo (32 em inglês, 63 em português e 25 em espanhol), 13 artigos no LILACS (10 em inglês, 2 em português e 1 em espanhol) e, por fim, 157 na PUBEMD (utilizando termos em inglês do MESH) sendo 140 em inglês, 17 em português. Após o processamento de dados, restaram 21 publicações. Conclusão: Foi possível evidenciar os prejuízos para o binômio mãe-bebê, mediante utilização da manobra de Kristeller na evolução normal do parto, com possibilidade de traumatizar física, psicológica e, até, emocionalmente a mãe

Extracellular Vesicles Released by Leishmania (Leishmania) amazonensis Promote Disease Progression and Induce the Production of Different Cytokines in Macrophages and B-1 Cells

The extracellular vesicles (EVs) released by Leishmania can contribute to the establishment of infection and host immunomodulation. In this study, we characterized the shedding of EVs from Leishmania (Leishmania) amazonensis promastigotes. This species is the causative agent of cutaneous leishmaniasis, and its role during interactions with bone marrow-derived macrophages (BMDMs) and peritoneal B-1 cells was evaluated. Leishmania amazonensis promastigotes cultivated in vitro at different times and temperatures spontaneously released EVs. EVs were purified using size-exclusion chromatography (SEC) and quantitated by nanoparticle tracking analysis (NTA). NTA revealed that the average size of the EVs was approximately 180 nm, with concentrations ranging from 1.8 × 108 to 2.4 × 109 vesicles/mL. In addition, the presence of LPG and GP63 were detected in EVs obtained at different temperatures. Naïve BMDMs stimulated with EVs exhibited increased IL-10 and IL-6 expression. However, incubating B-1 cells with parasite EVs did not stimulate IL-10 expression but led to an increase in the expression of IL-6 and TNFα. After 7 weeks post-infection, animals infected with L. amazonensis promastigotes in the presence of parasite EVs had significant higher parasite load and a polarization to Th2 response, as compared to the group infected with the parasite alone. This work demonstrated that EVs isolated from L. amazonensis promastigotes were able to stimulate macrophages and B-1 cells to express different types of cytokines. Moreover, the immunomodulatory properties of EVs probably contributed to an increase in parasite burden in mice. These findings suggest that the functionality of L. amazonensis EVs on immune system favor of parasite survival and disease progression

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

The BINGO project: II. Instrument description

Context. The measurement of diffuse 21-cm radiation from the hyperfine transition of neutral hydrogen (Hi signal) in different redshifts is an important tool for modern cosmology. However, detecting this faint signal with non-cryogenic receivers in single-dish telescopes is a challenging task. The BINGO (Baryon Acoustic Oscillations from Integrated Neutral Gas Observations) radio telescope is an instrument designed to detect baryonic acoustic oscillations (BAOs) in the cosmological Hi signal, in the redshift interval 0:127 ≤ z ≤ 0:449. Aims. This paper describes the BINGO radio telescope, including the current status of the optics, receiver, observational strategy, calibration, and the site. Methods. BINGO has been carefully designed to minimize systematics, being a transit instrument with no moving dishes and 28 horns operating in the frequency range 980 ≤ v ≤ 1260 MHz. Comprehensive laboratory tests were conducted for many of the BINGO subsystems and the prototypes of the receiver chain, horn, polarizer, magic tees, and transitions have been successfully tested between 2018-2020. The survey was designed to cover ∼13% of the sky, with the primary mirror pointing at declination δ = -15°. The telescope will see an instantaneous declination strip of 14:75. Results. The results of the prototype tests closely meet those obtained during the modeling process, suggesting BINGO will perform according to our expectations. After one year of observations with a 60% duty cycle and 28 horns, BINGO should achieve an expected sensitivity of 102μK per 9.33MHz frequency channel, one polarization, and be able to measure the Hi power spectrum in a competitive time frame

The BINGO project: I. Baryon acoustic oscillations from integrated neutral gas observations

Context. Observations of the redshifted 21-cm line of neutral hydrogen (HI) are a new and powerful window of observation that offers us the possibility to map the spatial distribution of cosmic HI and learn about cosmology. Baryon Acoustic Oscillations from Integrated Neutral Gas Observations (BINGO) is a new unique radio telescope designed to be one of the first to probe baryon acoustic oscillations (BAO) at radio frequencies. Aims. BINGO has two science goals: cosmology and astrophysics. Cosmology is the main science goal and the driver for BINGO's design and strategy. The key of BINGO is to detect the low redshift BAO to put strong constraints on the dark sector models and test the ICDM (cold dark matter) model. Given the versatility of the BINGO telescope, a secondary goal is astrophysics, where BINGO can help discover and study fast radio bursts (FRB) and other transients, as well as study Galactic and extragalactic science. In this paper, we introduce the latest progress of the BINGO project, its science goals, describing the scientific potential of the project for each goal and the new developments obtained by the collaboration. Methods. BINGO is a single dish transit telescope that will measure the BAO at low-z by making a 3D map of the HI distribution through the technique of intensity mapping over a large area of the sky. In order to achieve the project's goals, a science strategy and a specific pipeline for cleaning and analyzing the produced maps and mock maps was developed by the BINGO team, which we generally summarize here. Results. We introduce the BINGO project and its science goals and give a general summary of recent developments in construction, science potential, and pipeline development obtained by the BINGO Collaboration in the past few years. We show that BINGO will be able to obtain competitive constraints for the dark sector. It also has the potential to discover several FRBs in the southern hemisphere. The capacity of BINGO in obtaining information from 21-cm is also tested in the pipeline introduced here. Following these developments, the construction and observational strategies of BINGO have been defined. Conclusions. There is still no measurement of the BAO in radio, and studying cosmology in this new window of observations is one of the most promising advances in the field. The BINGO project is a radio telescope that has the goal to be one of the first to perform this measurement and it is currently being built in the northeast of Brazil. This paper is the first of a series of papers that describe in detail each part of the development of the BINGO project