293 research outputs found
Artery tertiary lymphoid organs control multi-layered territorialized atherosclerosis B cell responses in aged ApoE-/- mice
Objective: Explore aorta B cell immunity in aged ApoE-/- mice.
Approach and Results: Transcript maps, FACS, immunofluorescence analyses, cell transfers, and Ig-ELISPOT assays showed multi-layered atherosclerosis B cell responses in artery tertiary lymphoid organs (ATLOs). Aging-associated aorta B cell-related transcriptomes were identified and transcript atlases revealed highly territorialized B cell responses in ATLOs versus atherosclerotic lesions: ATLOs showed upregulation of bona fide B cell genes including Cd19, Ms4a1 (Cd20), Cd79a/b, and Ighm though intima plaques preferentially expressed molecules involved in non-B effector responses towards B cell-derived mediators, i.e. Fcgr3 (Cd16), Fcer1g (Cd23), and the C1q family. ATLOs promoted B cell recruitment. ATLO B-2 B cells included naïve, transitional, follicular, germinal center, switched IgG1+, IgA+, and IgE+ memory cells, plasmablasts, and long-lived plasma cells (PCs). ATLOs recruited large numbers of B-1 cells whose subtypes were skewed towards IL-10+ B-1b cells versus IL-10- B-1a cells. ATLO B-1 cells and PCs constitutively produced IgM and IgG and a fraction of PCs expressed IL-10. Moreover, ApoE-/- mice showed increased germinal center B cells in renal lymph nodes, IgM-producing PCs in the bone marrow, and higher IgM and anti-MDA-LDL IgG serum titers.
Conclusions: ATLOs orchestrate dichotomic, territorialized, and multi-layered B cell responses in the diseased aorta; germinal center reactions indicate generation of autoimmune B cells within the diseased arterial wall during aging
Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors
Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs
Recommended from our members
Patient ethnicity and three psychiatric intensive care units compared: the Tompkins Acute Ward Study
Background: Psychiatric Care Units provide care to disturbed patients in a context of higher security and staffing levels. Although such units are numerous, few systematic comparisons have been made, and there are indications that ethnic minority groups may be over-represented.
Aim: To compare the rates of adverse incidents and patterns of usage of three Psychiatric Intensive Care Units.
Method: The study used a triangulation or multi-method design, bringing together data from official statistics, local audit and interviews conducted with staff.
Results: Intensive care patients were more likely to be young, male, and suffering a psychotic disorder, as compared to general acute ward patients. Caribbean patients were twice as likely, and Asian patients half as likely, to receive intensive care (age, gender and diagnosis controlled). There were large differences in service levels, staffing, team functioning and adverse incidents between the three units. Various aspects of physical security were important in preventing absconds.
Conclusions: More evaluative research is required in order to define effective service levels, and to explore the nature of the interaction between ethnicity and inpatient care provision during acute illness
Abundances of the elements in the solar system
A review of the abundances and condensation temperatures of the elements and
their nuclides in the solar nebula and in chondritic meteorites. Abundances of
the elements in some neighboring stars are also discussed.Comment: 42 pages, 11 tables, 8 figures, chapter, In Landolt- B\"ornstein, New
Series, Vol. VI/4B, Chap. 4.4, J.E. Tr\"umper (ed.), Berlin, Heidelberg, New
York: Springer-Verlag, p. 560-63
The 22-Year Hale Cycle in cosmic ray flux: evidence for direct heliospheric modulation
The ability to predict times of greater galactic cosmic ray (GCR) fluxes is important for reducing the hazards caused by these particles to satellite communications, aviation, or astronauts. The 11-year solar-cycle variation in cosmic rays is highly correlated with the strength of the heliospheric magnetic field. Differences in GCR flux during alternate solar cycles yield a 22-year cycle, known as the Hale Cycle, which is thought to be due to different particle drift patterns when the northern solar pole has predominantly positive (denoted as qA>0 cycle) or negative (qA0 cycles than for qA0 and more sharply peaked for qA0 solar cycles, when the difference in GCR flux is most apparent. This suggests that particle drifts may not be the sole mechanism responsible for the Hale Cycle in GCR flux at Earth. However, we also demonstrate that these polarity-dependent heliospheric differences are evident during the space-age but are much less clear in earlier data: using geomagnetic reconstructions, we show that for the period of 1905 - 1965, alternate polarities do not give as significant a difference during the declining phase of the solar cycle. Thus we suggest that the 22-year cycle in cosmic-ray flux is at least partly the result of direct modulation by the heliospheric magnetic field and that this effect may be primarily limited to the grand solar maximum of the space-age
Effect of Magnetic-Field on the Microstructure and Macrosegregation in Directionally Solidified Pb-Sn Alloys
An investigation into the influence of a transverse magnetic field (0.45 T) on the mushy zone morphology and macrosegregation in directionally solidified hypoeutectic Pb-Sn alloy shows that the field has no influence on the morphology of dendritic arrays. The field does, however, cause severe distortion in the cellular array morphology. Cellular arrayed growth with the magnetic field results in an extensive channel formation in the mushy zone, as opposed to the well-aligned and uniformly distributed cells formed in the absence of the field. The channels are produced due to the anisotropy in the thermosolutal convection caused by the magnetic field. Macrosegregation, however, along the length of the directionally solidified samples is not influenced by this magnetic field for either the cellular or dendritic arrays
Observation of the rare decay K_S -> pi^0mu^+mu^-
A search for the decay K_S -> pi^0mu^+mu^- has been made by the NA48/1
Collaboration at the CERN SPS accelerator. The data were collected during 2002
with a high-intensity K_S beam. Six events were found with a background
expectation of 0.22^+0.18_-0.11 event. Using a vector matrix element and unit
form factor, the measured branching ratio is B(K_S ->
pi^0mu^+mu^-)=[2.9^+1.5_-1.2(stat)+/-0.2(syst)]x10^{-9}.Comment: 19 pages, 8 figures, 4 tables. To be published in Physics Letters
First Observation and Measurement of the Decay K+- -> pi+- e+ e- gamma
Using the full data set of the NA48/2 experiment, the decay K+- -> pi+- e+ e-
gamma is observed for the first time, selecting 120 candidates with 7.3 +- 1.7
estimated background events. With K+- -> pi+- pi0D as normalisation channel,
the branching ratio is determined in a model-independent way to be Br(K+- ->
pi+- e+ e- gamma, m_eegamma > 260 MeV/c^2) = (1.19 +- 0.12_stat +- 0.04_syst) x
10^-8. This measured value and the spectrum of the e+ e- gamma invariant mass
allow a comparison with predictions of Chiral Perturbation Theory.Comment: 13 pages, 3 figures. Accepted for publication in Phys.Lett.
First observation and branching fraction and decay parameter measurements of the weak radiative decay Xi0 --> Lambda e+e-
The weak radiative decay Xi0 --> Lambda e+e- has been detected for the first
time. We find 412 candidates in the signal region, with an estimated background
of 15 +/- 5 events. We determine the branching fraction B(Xi0 --> Lambda e+e-)
= [7.6 +/- 0.4(stat) +/- 0.4(syst) +/- 0.2(norm)] x 10^{-6}, consistent with an
internal bremsstrahlung process, and the decay asymmetry parameter
alpha_{XiLambdaee} = -0.8 +/- 0.2, consistent with that of Xi0 --> Lambda
gamma. The charge conjugate reaction Xi0_bar --> Lambda_bar e+e- has also been
observed.Comment: 20 pages, 5 figures, 4 tables; revised: 19 pages, 4 figures, 4
tables, after reviewers' comments: 1 figure removed, 1 figure corrected,
minor editorial changes; to be published in Phys. Lett.
- …