The Role of Chemokines in Mediating Graft Versus Host Disease: Opportunities for Novel Therapeutics

Bone marrow transplantation (BMT) is the current therapy of choice for several malignancies and severe autoimmune diseases. Graft versus host disease (GVHD) is the major complication associated with BMT. T lymphocytes and other leukocytes migrate into target organs during GVHD, become activated and mediate tissue damage. Chemokines are well known inducers of leukocyte trafficking and activation and contribute to the pathogenesis of GVHD. Here, we review the major animal models used to study GVHD and the role of chemokines in mediating tissue damage in these models. The role of these molecules in promoting potential beneficial effects of the graft, especially graft versus leukemia, is also discussed. Finally, the various pharmacological strategies to block the chemokine system or downstream signaling events in the context of GVHD are discussed

Effects of flares on solar high-degree helioseismic acoustic mode amplitudes

Several attempts have been made to observe whether solar flares excite acoustic modes since Wolff (1972) suggested this possibility. We look for the impact of flares on the amplitude of solar acoustic modes and other effects that are also affecting the mode amplitude. Solar acoustic mode amplitudes are known to be sensitive to magnetic fields. As flares usually occur in the presence of strong magnetic fields and most likely are the by-product of magnetic reconnection, we show how the magnetic field in and around the flaring region affects the mode amplitude. The mode amplitudes were obtained using ring-diagram analysis, which was first applied to a single event, the largest flare in the space age (the `Halloween Flare', SOL2003-10-28T11:00), using MDI data. Then, using HMI data, the analysis was applied to the regions corresponding to the flares observed during the high activity phase of cycle 24 and that fall into two groups. These two groups consist of small (10-60 erg cm$^{-2}$ s$^{-1}$) and large ($>$1200 erg cm$^{-2}$ s$^{-1}$) peak-flux flares, based on the Heliophysics Event Knowledgebase (HEK). The first set is used as a comparison to the results of the strong flares in the second set. After applying several corrections in order to take into account several sources of bias, we did not find any amplification in the inferred mode amplitude due to flaring activity larger than a 10% uncertainty.Comment: Submitted to MNRA

Resolution of inflammation: Mechanisms and opportunity for drug development

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The role of CCL22 (MDC) for the recruitment of eosinophils during allergic pleurisy in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142274/1/jlb0356.pd

Acute exercise in treated phenylketonuria patients:Physical activity and biochemical response

Background: In phenylketonuria, dietary treatment prevents most of the severe brain disease. However, patients have to follow a diet restricted in several natural components, what may cause decreased bone density and obesity. Exercise is known to improve both mental functioning and bone density also avoiding obesity, and could optimize aspects of central and peripheral outcome, regardless changes in phenylalanine (Phe) levels. However, the acute effects of exercise on metabolic parameters in phenylketonuria patients are unknown and thereby long-term adaptations are unclear. Therefore, this study aimed to evaluate patients' basal metabolic rate (BMR), and their acute response to an aerobic exercise session on plasma concentrations of Phe, tyrosine (Tyr), and branched-chain amino acids (BCAA), as well as metabolic and hormonal responses. Methods: Five early- and four late diagnosed phenylketonuria patients aged 21 ± 4 years and 17 sex-, age-, and BMI-matched controls were evaluated for BMR, peak oxygen consumption (VO2peak) and plasma amino acid, glucose, lipid profile and hormonal levels. At least one week later, participants performed a 30-min aerobic exercise session (intensities individually calculated using the VO2peak results). Blood samples were collected in fasted state (moment 1, M1) and immediately after a small breakfast, which included the metabolic formula for patients but not for controls, and the exercise session (moment 2, M2). Results: Phenylketonuria patients and controls showed similar BMR and physical capacities. At M1, patients presented higher Phe concentration and Phe/Tyr ratio; and lower levels of BCAA and total cholesterol than controls. Besides that, poorly controlled patients tended to stay slightly below the prescribed VO2 during exercise. Both patients and controls showed increased levels of total cholesterol and LDL at M2 compared with M1. Only controls showed increased levels of Tyr, lactate, and HDL; and decreased Phe/Tyr ratio and glucose levels at M2 compared to values at M1. Conclusions: Acute aerobic exercise followed by a Phe-restricted breakfast did not change Phe concentrations in treated phenylketonuria patients, but it was associated with decreased Phe/Tyr only in controls. Further studies are necessary to confirm our results in a higher number of patients

The protein LJM 111 from Lutzomyia longipalpis Salivary Gland Extract (SGE) accounts for the SGE-inhibitory effects upon inflammatory parameters in experimental arthritis model

Several studies have pointed out the immunomodulatory properties of the Salivary Gland Extract (SGE) from Lutzomyia longipalpis. We aimed to identify the SGE component (s) responsible for its effect on ovalbumin (OVA)-induced neutrophil migration (NM) and to evaluate the effect of SGE and components in the antigen-induced arthritis (AIA) model. We tested the anti-arthritic activities of SGE and the recombinant LJM111 salivary protein (rLJM111) by measuring the mechanical hypernociception and the NM into synovial cavity. Furthermore, we measured IL-17, TNF-alpha and IFN-gamma released by lymph nodes cells stimulated with mBSA or anti-CD3 using enzyme-linked immunosorbent assay (ELISA). Additionally, we tested the effect of SGE and rLJM111 on co-stimulatory molecules expression (MHC-II and CD-86) by flow cytometry. TNF-alpha and IL-10 production (ELISA) of bone marrow-derived dendritic cells (BMDCs) stimulated with LPS, chemotaxis and actin polymerization from neutrophils. Besides, the effect of SGE on CXCR2 and GRK-2 expression on neutrophils was investigated. We identified one plasmid expressing the protein LJM111 that prevented NM in OVA-challenged immunized mice. Furthermore, both SGE and rLJM111 inhibited NM and pain sensitivity in AIA and reduced IL-17, TNF-alpha and IFN-gamma. SGE and rLJM111 also reduced MHC-II and CD-86 expression and TNF-alpha whereas increased IL-10 release by LPS-stimulated BMDCs. SGE, but not LJM 111, inhibited neutrophils chemotaxis and actin polymerization. Additionally, SGE reduced neutrophil CXCR2 expression and increased GRK-2. Thus, rLJM111 is partially responsible for SGE mechanisms by diminishing DC function and maturation but not chemoattraction of neutrophils. (C) 2012 Elsevier B.V. All rights reserved

Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross-Cultural Adaptation and Validation Study

Background Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2 /df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2 /df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). Themodel exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2 : λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2 : λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2 : λ: p = .058; i: p < .001; Res: p < .001). Conclusion The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatment

VISIONS: The VISTA Star Formation Atlas -- I. Survey overview

© The Authors 2023. Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0).VISIONS is an ESO public survey of five nearby (d < 500 pc) star-forming molecular cloud complexes that are canonically associated with the constellations of Chamaeleon, Corona Australis, Lupus, Ophiuchus, and Orion. The survey was carried out with VISTA, using VIRCAM, and collected data in the near-infrared passbands J, H, and Ks. With a total on-sky exposure time of 49.4 h VISIONS covers an area of 650 deg$^2$, and it was designed to build an infrared legacy archive similar to that of 2MASS. Taking place between April 2017 and March 2022, the observations yielded approximately 1.15 million images, which comprise 19 TB of raw data. The observations are grouped into three different subsurveys: The wide subsurvey comprises shallow, large-scale observations and has visited the star-forming complexes six times over the course of its execution. The deep subsurvey of dedicated high-sensitivity observations has collected data on the areas with the largest amounts of dust extinction. The control subsurvey includes observations of areas of low-to-negligible dust extinction. Using this strategy, the VISIONS survey offers multi-epoch position measurements, is able to access deeply embedded objects, and provides a baseline for statistical comparisons and sample completeness. In particular, VISIONS is designed to measure the proper motions of point sources with a precision of 1 mas/yr or better, when complemented with data from VHS. Hence, VISIONS can provide proper motions for sources inaccessible to Gaia. VISIONS will enable addressing a range of topics, including the 3D distribution and motion of embedded stars and the nearby interstellar medium, the identification and characterization of young stellar objects, the formation and evolution of embedded stellar clusters and their initial mass function, as well as the characteristics of interstellar dust and the reddening law.Peer reviewe

VISIONS:the VISTA Star Formation Atlas I. Survey overview

VISIONS is an ESO public survey of five nearby (d &lt; 500 pc) star-forming molecular cloud complexes that are canonically associated with the constellations of Chamaeleon, Corona Australis, Lupus, Ophiuchus, and Orion. The survey was carried out with the Visible and Infrared Survey Telescope for Astronomy (VISTA), using the VISTA Infrared Camera (VIRCAM), and collected data in the near-infrared passbands J (1.25 μm), H (1.65 μm), and KS (2.15 μm). With a total on-sky exposure time of 49.4h VISIONS covers an area of 650 deg2, it is designed to build an infrared legacy archive with a structure and content similar to the Two Micron All Sky Survey (2MASS) for the screened star-forming regions. Taking place between April 2017 and March 2022, the observations yielded approximately 1.15 million images, which comprise 19 TB of raw data. The observations undertaken within the survey are grouped into three different subsurveys. First, the wide subsurvey comprises shallow, large-scale observations and it has revisited the star-forming complexes six times over the course of its execution. Second, the deep subsurvey of dedicated high-sensitivity observations has collected data on areas with the largest amounts of dust extinction. Third, the control subsurvey includes observations of areas of low-to-negligible dust extinction. Using this strategy, the VISIONS observation program offers multi-epoch position measurements, with the ability to access deeply embedded objects, and it provides a baseline for statistical comparisons and sample completeness – all at the same time. In particular, VISIONS is designed to measure the proper motions of point sources, with a precision of 1 mas yr−1 or better, when complemented with data from the VISTA Hemisphere Survey (VHS). In this way, VISIONS can provide proper motions of complete ensembles of embedded and low-mass objects, including sources inaccessible to the optical ESA Gaia mission. VISIONS will enable the community to address a variety of research topics from a more informed perspective, including the 3D distribution and motion of embedded stars and the nearby interstellar medium, the identification and characterization of young stellar objects, the formation and evolution of embedded stellar clusters and their initial mass function, as well as the characteristics of interstellar dust and the reddening law