2,468 research outputs found
Immune regulatory networks coordinated by glycans and glycan-binding proteins in autoimmunity and infection
The immune system is coordinated by an intricate network of stimulatory and inhibitory circuits that regulate host responses against endogenous and exogenous insults. Disruption of these safeguard and homeostatic mechanisms can lead to unpredictable inflammatory and autoimmune responses, whereas deficiency of immune stimulatory pathways may orchestrate immunosuppressive programs that contribute to perpetuate chronic infections, but also influence cancer development and progression. Glycans have emerged as essential components of homeostatic circuits, acting as fine-tuners of immunological responses and potential molecular targets for manipulation of immune tolerance and activation in a wide range of pathologic settings. Cell surface glycans, present in cells, tissues and the extracellular matrix, have been proposed to serve as âself-associated molecular patternsâ that store structurally relevant biological data. The responsibility of deciphering this information relies on different families of glycan-binding proteins (including galectins, siglecs and C-type lectins) which, upon recognition of specific carbohydrate structures, can recalibrate the magnitude, nature and fate of immune responses. This process is tightly regulated by the diversity of glycan structures and the establishment of multivalent interactions on cell surface receptors and the extracellular matrix. Here we review the spatiotemporal regulation of selected glycan-modifying processes including mannosylation, complex Nglycan branching, core 2 O-glycan elongation, LacNAc extension, as well as terminal sialylation and fucosylation. Moreover, we illustrate examples that highlight the contribution of these processes to the control of immune responses and their integration with canonical tolerogenic pathways. Finally, we discuss the power of glycans and glycan-binding proteins as a source of immunomodulatory signals that could be leveraged for the treatment of autoimmune inflammation and chronic infection.This work was supported by grants from SSP: co-funded by the European Union (ERC, GlycanSwitch, 101071386). Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. The work was also co-funded by EU GlycanTrigger-grant Agreement No: 101093997. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. SSP also acknowledges funding by â2022 LRA Lupus Innovation Awardâ and by âEuropean Crohnâs and Colitis Organisation (ECCO) Pioneer Award 2021â. SSP also acknowledges the US Department of Defense, US Army Medical Research Acquisition Activity, FY18 Peer Reviewed Medical Research Program Investigator-Initiated Research Award (award number W81XWH1920053) as well as grant funded by the Portuguese Foundation for Science and Technology â FCT (EXPL/MED-ONC/0496/2021). IA acknowledges FCT for funding (2022.00337.CEECIND). JG acknowledges funding from ESCMID (ESCMID Research Grant 2022), ECCO (ECCO Grant 2023) and FCT (2020.00088.CEECIND). G.A.R acknowledges grants from the Argentinean Agency for Promotion of Science, Technology and Innovation (PICT 2017-0494, PICT-FBB 620 and PICT 2020-01552). The authors are also thankful for generous support from Sales
(Argentina), Bunge & Born (Argentina), Baron (Argentina), Williams (Argentina) and Richard Lounsbery (USA) Foundations, as well as donations from Ferioli-Ostry and Caraballo families to GAR
Toxicity of copaiba extracts to armyworm (Spodoptera frugiperda)
The objective of this study was to evaluate the effects of methanolic extracts from leaves, peels, seeds and pulps from fruits of Copaifera langsdorffii on Spodoptera frugiperda. Extracts derived from leaves and fruit peels were more toxic to S. frugiperda than the others. Hence, they were added to the artificial diet and used in further experiments with the second instar larvae of the insect, which presented larval growth reduction, prolonged period of development, increased mortality, and lower fertility and fecundity of adults. Lower egg viability was also observed when the insect was treated with extracts of leaves and fruit peels in the larvae stage. Moreover, when subjected to ultrastructural analysis under a scanning electron microscope, such eggs showed abnormalities in the aeropylar and micropylar regions. Both extracts also increased the excretion of protein in the insect feces and inhibited trypsin activity in the in vitro test. Consequently, C. langsdorffii presents potential to be used in the development of new products to control the fall armyworm.Key words: Copaifera langsdorffii, natural products, trypsin inhibitor, botanical insecticide
Delay in maturation of the submandibular gland in Chagas disease correlates with lower DNA synthesis
Vector competence of Culex quinquefasciatus Say, 1823 exposed to different densities of microfilariae of Dirofilaria immitis (Leidy,1856)
Vector competence of Cuter quinquefascictus Say, 1823 exposed to different densities of microfilariae of Dirofilaria immitis (Leidy, 1856). The metropolitan region of Recife, Brazil is endemic for Dirofilaria immitis and has an environment favorable to the development of Culex quinquefasciatus. The goal of this study was to evaluate the vector competence of the Cx. quinquefasciatus RECIFE population for D. immitis transmission. A total of 2.104 females of Cx. quinquefasciatus RECIFE population were exposed to different densities of D. immitis microfilariae blood meals, ranging from 1,820 to 2,900 mf/ml of blood, in a natural membrane apparatus. The results showed a variation between 92.3% and 98.8% of females fed. The exposure of the Cx. quinquefasciatus RECIFE population to different densities of microfilariac did not influence the mortality of the mosquitoes. Infective larvae from D. immitis were observed in the Malpighian tubules beginning on the 12(th) day, whereas larvae were observed in the head and proboscis beginning oil the 13(th) day following infection. The vector efficiency index (VEI) presented by the mosquitoes ranged front 7.8 to 56.5. The data demonstrates that the Cx. quinquefasciatus RECIFE population has great potential for the transmission of D. immitis, as it allowed the development of the filarid until the infectious stage at the different densities of microfilariae to which it was exposed.52465866
Detection and Antimicrobial Resistance Profile of Enteropathogenic (EPEC) and Shigatoxigenic Escherichia coli (STEC) in Conventional and Organic Broiler Chickens
ABSTRACT Enteropatogenic Escherichia coli (EPEC) and shigatoxigenic E. coli (STEC), are generally poultry and poultry product isolate and can cause serious human infections. Many strains may become resistant to various antimicrobials, which can hinder the treatment of bacterial diseases. Organic farming seeks to avoid the selection and frequency of antimicrobial-resistant bacteria. This study aims to verify the resistance of EPEC and STEC from organic and conventional (industrial) broiler isolates to antimicrobials. All isolates were submitted to disk diffusion test with tetracycline, gentamicin, enrofloxacin, ceftriaxone and amoxicillin + clavulanate (TET, GEN, ENO, CTX, AMC) and PCR to detect specific virulence genes for EPEC and STEC. A total of 297 E. coli strains were isolated, 213 from conventional. In organic broiler, 84 strains were isolated. The strains from the conventional broiler isolates were resistant to five antimicrobials tested: TET 48.82% (104/213), ENO 28.17% (60/213), CTX 15.49% (33/213), GEN 14.55% (31/213), and AMC 7.04% (15/213), and 9.86% (21/213) were considered multidrug-resistant. Organic chicken strains were resistant to four of the antimicrobials tested: TET 35.7% (30/84), ENO 9.5% (8/84), CTX 2.4% (2/84), GEN 4.8% (4/84). Of the strains from the organic broiler chicken isolates, only 1.2% (1/84) was considered multidrug-resistant. No EPEC and STEC were found in the organic chicken samples. The multidrug resistance was characterized in 9.52% (2/21) of the EPEC and 4.76% (1/21) of the STEC. The study demonstrated the absence of EPEC and STEC strains in organic broilers and carcasses and a lower frequency of multiresistant strains compared to conventional breeding
Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity
T-cell development ensures the formation of diverse repertoires of T-cell receptors (TCRs) that recognize a variety of antigens. Glycosylation is a major posttranslational modification present in virtually all cells, including T-lymphocytes, that regulates activity/functions. Although these structures are known to be involved in TCR-selection in DP thymocytes, it is unclear how glycans regulate other thymic development processes and how they influence susceptibility to disease. Here, we discovered stage-specific glycome compositions during T-cell development in human and murine thymocytes, as well as dynamic alterations. After restricting the N-glycosylation profile of thymocytes to high-mannose structures, using specific glycoengineered mice (Rag1CreMgat1fl/fl), we showed remarkable defects in key developmental checkpoints, including Ă-selection, regulatory T-cell generation and γΎT-cell development, associated with increased susceptibility to colon and kidney inflammation and infection. We further demonstrated that a single N-glycan antenna (modeled in Rag1CreMgat2fl/fl mice) is the sine-qua-non condition to ensure normal development. In conclusion, we revealed that mannosylated thymocytes lead to a dysregulation in T-cell development that is associated with inflammation susceptibility.Funded by the â2022 Lupus Research Alliance (LRA) Lupus Innovation Awardâ. Institutional funding from the Portuguese Foundation for Science and Technology (FCT): projects NORTE-01-0145-FEDER-000029, POCI-01/0145-FEDER-016601, POCI-01-0145-FEDER-028772, and PTDC/MEC-REU/28772/2017 (SSP). This study was co-funded by the European Union (ERC Synergy, GlycanSwitch, 101071386). Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. The study was also co-funded by the European Union, GlycanTrigger project, Grant Agreement No: 101093997. Views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. A grant was received from the Portuguese group of study in autoimmune diseases (NEDAI) to SSP. MMV (PD/BD/135452/2017; COVID/BD/152488/2022) received funding from the FCT
Catastrophizing mediates the relationship between the personal belief in a just world and pain outcomes among chronic pain support group attendees
Health-related research suggests the belief in a just world can act as a personal resource that protects against the adverse effects of pain and illness. However, currently, little is known about how this belief, particularly in relation to oneâs own life, might influence pain. Consistent with the suggestions of previous research, the present study undertook a secondary data analysis to investigate pain catastrophizing as a mediator of the relationship between the personal just world belief and chronic pain outcomes in a sample of chronic pain support group attendees. Partially supporting the hypotheses, catastrophizing was negatively correlated with the personal just world belief and mediated the relationship between this belief and pain and disability, but not distress. Suggestions for future research and intervention development are made
Search for new neutral Higgs bosons through the H â ZAâ â+ââb b ÂŻ process in pp collisions at âs = 13 TeV
This paper reports on a search for an extension to the scalar sector of the standard model, where a new CP-even (odd) boson decays to a Z boson and a lighter CP-odd (even) boson, and the latter further decays to a b quark pair. The Z boson is reconstructed via its decays to electron or muon pairs. The analysed data were recorded in proton-proton collisions at a center-of-mass energy s = 13 TeV, collected by the CMS experiment at the LHC during 2016, corresponding to an integrated luminosity of 35.9 fbâ1. Data and predictions from the standard model are in agreement within the uncertainties. Upper limits at 95% confidence level are set on the production cross section times branching fraction, with masses of the new bosons up to 1000 GeV. The results are interpreted in the context of the two-Higgs-doublet model. [Figure not available: see fulltext.]
The Hubble Constant
I review the current state of determinations of the Hubble constant, which
gives the length scale of the Universe by relating the expansion velocity of
objects to their distance. There are two broad categories of measurements. The
first uses individual astrophysical objects which have some property that
allows their intrinsic luminosity or size to be determined, or allows the
determination of their distance by geometric means. The second category
comprises the use of all-sky cosmic microwave background, or correlations
between large samples of galaxies, to determine information about the geometry
of the Universe and hence the Hubble constant, typically in a combination with
other cosmological parameters. Many, but not all, object-based measurements
give values of around 72-74km/s/Mpc , with typical errors of 2-3km/s/Mpc.
This is in mild discrepancy with CMB-based measurements, in particular those
from the Planck satellite, which give values of 67-68km/s/Mpc and typical
errors of 1-2km/s/Mpc. The size of the remaining systematics indicate that
accuracy rather than precision is the remaining problem in a good determination
of the Hubble constant. Whether a discrepancy exists, and whether new physics
is needed to resolve it, depends on details of the systematics of the
object-based methods, and also on the assumptions about other cosmological
parameters and which datasets are combined in the case of the all-sky methods.Comment: Extensively revised and updated since the 2007 version: accepted by
Living Reviews in Relativity as a major (2014) update of LRR 10, 4, 200
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