510 research outputs found
Ly9 (CD229) cell surface receptor is crucial for the development of spontaneous autoantibody production to nuclear antigens
The Signaling Lymphocyte Activation Molecule Family (SLAMF) genes, which encode cell-surface receptors that modulate innate and adaptive immune responses, lay within a genomic region of human and mouse chromosome 1 that confers a predisposition for the development of systemic lupus erythematosus (SLE). Herein, we demonstrate that the SLAMF member Ly9 arises as a novel receptor contributing to the reinforcement of tolerance. Specifically, Ly9-deficient mice spontaneously developed features of systemic autoimmunity such as the production of anti-nuclear antibodies (ANA), -dsDNA, and -nucleosome autoantibodies, independently of genetic background [(B6.129) or (BALB/c.129)]. In aged (10- to 12-month-old) Ly9 (-/-) mice key cell subsets implicated in autoimmunity were expanded, e.g., T follicular helper (Tfh) as well as germinal center (GC) B cells. More importantly, in vitro functional experiments showed that Ly9 acts as an inhibitory receptor of IFN-γ producing CD4(+) T cells. Taken together, our findings reveal that the Ly9 receptor triggers cell intrinsic safeguarding mechanisms to prevent a breach of tolerance, emerging as a new non-redundant inhibitory cell-surface receptor capable of disabling autoantibody responses
Photodynamic Therapy for the Treatment of Complex Anal Fistula
Background and objectives: To validate and analyze the results of intralesional photodynamic therapy in the treatment of complex anal fistula.
Study design/materials and methods: This prospective multicentric observational study enrolled patients treated for complex anal fistula who underwent intralesional photodynamic therapy (i-PDT). The included patients were treated from January 2016 to December 2018 with a minimum follow-up of 1 year to evaluate recurrence, continence and postoperative morbidity. Intralesional 5-aminolevulinic acid (ALA) gel (2%) was injected directly into the fistula. The internal and external orifices were closed. After an incubation period of 2 hours, the fistula was irradiated using an optical fiber connected to a red laser (Multidiode 630 PDT) operating at 1 W/cm for 3 minutes (180 J).
Results: In total, 49 patients were included (61.2% male). The mean age was 48 years, and the mean duration of fistula was 13 months. Of the fistulas included, 75.5% were medium transphincteric, and 24.5% were high transphincteric. The median fistula length was 4 ± 1,14 cm (range: 3-5). A total of 41 patients (83.7%) had a previous history of fistula surgery. Preoperatively, some degree of anal incontinence was found in 5 patients (10.2%). No center reported any other procedure-related complications intraoperatively. Phototoxicity was found in one patient. In the first 48 hours after the procedure, fever was reported in 2 patients (4%). At the end of follow-up, total healing was observed in 32/49 patients (65.3%). No patient reported new incontinence postoperatively.
Conclusion: i-PDT could be considered a good choice in patients with complex anal fistulas to avoid surgery and its complications. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc
Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial
Objective:
To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms.
Design:
An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used.
Setting:
Spanish older adults with metabolic syndrome (MetS).
Participants:
A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS.
Results:
Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)).
Conclusions:
According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.T The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research Grant 2013-2018; 340918) grant to Miguel Angel Martinez-Gonzalez, and by the official funding agency for biomedical research of the Spanish Government, ISCIII through the Fondo de Investigacion para la Salud (FIS), which is cofunded by the European Regional Development Fund (four coordinated FIS projects led by Jordi Salas-Salvado and Josep Vidal), including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, The Especial Action Project entitled: 'Implementacion y Evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus' grant to Jordi Salas-Salvado, the Recercaixa grant to Jordi Salas-Salvado (2013ACUP00194), grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant, and CIBEROBN and FEDER funds (CB06/03), ISCIII. International Nut&Dried Fruit Council-FESNAD N degrees 201302: Miguel Angel Martinez-Gonzalez (PI). None of the funding sources took part in the design, collection, analysis or interpretation of the data, or in the decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and had final responsibility to submit for publication
Dietary diversity and Depression: Cross-sectional and longitudinal analyses in Spanish adult population with Metabolic Syndrome. Findings from PREDIMED-PLUS Trial.
Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between Dietary Diversity (DD) and depressive symptoms. Design: An energy-adjusted Dietary Diversity Score (DDS) was assessed using a validated food-frequency questionnaire and was categorized into quartiles (Q). The variety in each food group was classified into 4 categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II>=18. Linear and logistic regression models were used. Setting: Spanish older adults with Metabolic Syndrome. Participants: A total of 6625 adults aged (55-75 years) from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; Odds Ratio (OR) Q4 vs Q1= 0.76 (95% confidence interval (CI): 0.64, 0.90). This was driven by high diversity compared to low diversity (C3 vs. C1) of vegetables [OR (95%CI) = 0.75 (0.57, 0.93)], cereals [OR (95%CI) = 0.72 (0.56-0.94)] and proteins [OR (95%CI) = 0.27 (0.11, 0.62)]. In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 y- of follow-up, except for DD in vegetables C4 vs C1= [β (95%CI) = 0.70 (0.05, 1.35)]. Conclusions: According to our results, DD is associated with the presence of depressive symptoms but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up period) are needed to confirm these findings
Multidifferential study of identified charged hadron distributions in -tagged jets in proton-proton collisions at 13 TeV
Jet fragmentation functions are measured for the first time in proton-proton
collisions for charged pions, kaons, and protons within jets recoiling against
a boson. The charged-hadron distributions are studied longitudinally and
transversely to the jet direction for jets with transverse momentum 20 GeV and in the pseudorapidity range . The
data sample was collected with the LHCb experiment at a center-of-mass energy
of 13 TeV, corresponding to an integrated luminosity of 1.64 fb. Triple
differential distributions as a function of the hadron longitudinal momentum
fraction, hadron transverse momentum, and jet transverse momentum are also
measured for the first time. This helps constrain transverse-momentum-dependent
fragmentation functions. Differences in the shapes and magnitudes of the
measured distributions for the different hadron species provide insights into
the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any
supplementary material and additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb
public pages
Study of the decay
The decay is studied
in proton-proton collisions at a center-of-mass energy of TeV
using data corresponding to an integrated luminosity of 5
collected by the LHCb experiment. In the system, the
state observed at the BaBar and Belle experiments is
resolved into two narrower states, and ,
whose masses and widths are measured to be where the first uncertainties are statistical and the second
systematic. The results are consistent with a previous LHCb measurement using a
prompt sample. Evidence of a new
state is found with a local significance of , whose mass and width
are measured to be and , respectively. In addition, evidence of a new decay mode
is found with a significance of
. The relative branching fraction of with respect to the
decay is measured to be , where the first
uncertainty is statistical, the second systematic and the third originates from
the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb
public pages
Measurement of the ratios of branching fractions and
The ratios of branching fractions
and are measured, assuming isospin symmetry, using a
sample of proton-proton collision data corresponding to 3.0 fb of
integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The
tau lepton is identified in the decay mode
. The measured values are
and
, where the first uncertainty is
statistical and the second is systematic. The correlation between these
measurements is . Results are consistent with the current average
of these quantities and are at a combined 1.9 standard deviations from the
predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb
public pages
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
Estudi de receptors leucocitaris de la família del CD150. Identificació i caracterització dels lligands de CD84 i CD229
[cat] La família del CD150 es troba constituïda per nou proteïnes expressades en la superficie dels leucòcits implicades en l'activació dels limfòcits i que pertanyen a la superfamília de les immunoglobulines. Els receptors CD84, CD150 (SLAM), CD229 (Ly9), CD244 (2B4), NTB-A i CS1 s'associen amb els adaptadors SAP ( SLAM-associated protein) i EAT-2. L'adaptador SAP és una proteïna intracel·lular que es troba mutada en malalts amb el síndrome d'immunodeficiència lligat al cromosoma X (XLP). Aquest estudi s'ha analizat l'expressió de CD84, CD150, CD229 i CD244 en diferents leucòcits i poblacions limfocitàries mitjançant citometria de fluxe. El CD84 i el CD150 estaven presents en timòcits, cèl·lules T madures i cèl·lules presentadores d'antígen. L'expressió de CD84 i CD150 era elevada en cél·lules T memòria. L'expressió de CD150 s'incrementava molt després de l'activació. Al contrari que el CD84, el CD150 es trobava absent en monòcits en repòs i en cèl·lules dendrítiques immadures. El CD229 presentava un patró d'expressió restringit a limfòcits. El CD244 s'expressava de forma preferencial en cèl·lules NK, limfòcits CD8+ efectors, monòcits en repòs, basòfils i eosinòfils. Nosaltres hem descrit una distribució de CD84, CD150, CD229 i CD244 més àmplia que la prèviament descrita i hem demostrat que aquestes molècules s'expressen de forma diferencial en les cèl·lules hematopoiètiques. L'expressió heterogènea d'aquests receptors indica que deuen tenir funcions no redundants en la regulació tant del sistema immune adaptatiu com de l'innat. Amb la finalitat d'identificar el lligand de CD84, es va generar una proteïna de fusió soluble constituïda pels dominis extracel·lulars de CD84 i dos dominis immunoglobulina constants de la IgG humana (CD84-Ig). Degut a que ja havien estat descrites diverses interaccions entre membres de la mateixa família CD2 / CD150, es va assajar la interacció de la proteïna de fusió CD84-Ig amb cèl·lules COS transfectades amb els cDNAs de diferents membres de la família CD2 / CD150. La proteïna de fusió CD84-Ig interaccionava amb cèl·lules transfectades amb el cDNA de CD84, però no s'observava cap interacció amb la resta de membres de la família del CD2 / CD150. Així doncs, el CD84 interaccionava amb ell mateix. Els anticossos contra CD84 que reconeixien el primer domini V-like, bloquejaven la interacció de la proteïna de fusió de CD84 en les cèl·lules transfectades amb el cDNA de CD84 i en plaquetes. A més a més, els resultats obtinguts amb quimeres humà / murí dels dominis extracel·lulars de CD84, demostren que únicament el primer domini extracel·lular N-terminal és el responsable de la interacció homofílica. La interacció CD84-CD84 és independent de la seva cua citoplasmàtica. Finalment, la co-lligació del CD84 amb anticossos contra CD84 o la proteïna de fusió CD84-Ig i anticossos contra CD3, incrementen la secreció de IFN-gamma en limfòcits humans. Així, CD84 interacciona de manera homotípica i actua com a molècula coestimuladora. Amb l'objectiu d'indentificar el lligand de CD229, es va generar una proteïna de fusió soluble que contenia els dos dominis Ig N-terminals del receptor CD229 (CD229-Ig). La proteïna de fusió CD229-Ig s'unia a les cèl·lules transfectades amb el cDNA de CD229 però no es va detectar cap interacció amb les cèl·lules que expressaven la resta dels membres de la família del CD150, demostrant així que CD229 interaccionava de manera homofílica. Tant el CD229 humà com el de ratolí interaccionen amb ells mateixos. Amb mutants en que es deleccionaven els dominis Ig es va demostrar que el domini immunoglobulina N-terminal mitjançava l'adhesió homofílica. La interacció CD229-CD229 es veia severament compromesa quan es mutaven tres aminoàcids carregats del domini Ig N-terminal: E27 i E29 en el "loop" B-C i R89 en el "loop" F-G, localitzacions predites mitjançant anàlisi computacional. De manera sorprenent, la mutació R44A augmentava la interacció homofílica. Imatges obtingudes per microscopia confocal revelaven que el CD229 es relocalizava en les zones de contacte entre les cèl·lules B i T durant la formació de la sinapsi immunològica. Per tant, CD229 interacciona de forma homotípica i participa en la sinapsi immunològica
Innate Lymphoid Cells (ILCs): Cytokine Hubs Regulating Immunity and Tissue Homeostasis
Innate lymphoid cells (ILCs) have emerged as an expanding family of effector cells particularly enriched in the mucosal barriers. ILCs are promptly activated by stress signals and multiple epithelial- and myeloid-cell-derived cytokines. In response, ILCs rapidly secrete effector cytokines, which allow them to survey and maintain the mucosal integrity. Uncontrolled action of ILCs might contribute to tissue damage, chronic inflammation, metabolic diseases, autoimmunity, and cancer. Here we discuss the recent advances in our understanding of the cytokine network that modulate ILC immune responses: stimulating cytokines, signature cytokines secreted by ILC subsets, autocrine cytokines, and cytokines that induce cell plasticit
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