798 research outputs found
When resistance is useless: policing and the evolution of reproductive acquiescence in insect societies
In social groups composed of kin, inclusive fitness benefits can favor greater cooperation. Alternatively, cooperation can be enforced through the policing of less cooperative individuals. Here, we show that the effect of policing can be twofold: not only can it directly suppress individual selfishness, it can also entirely remove the incentive for individuals to act selfishly in the first place. We term such individual restraint in response to socially imposed policing "acquiescence" and illustrate the concept using examples drawn from the social Hymenoptera (the ants, bees, and wasps). Inclusive fitness models confirm that when a policing system is in place, individuals should be less tempted to act selfishly. This is shown to have important consequences for the resolution of conflict within their societies. For example, it can explain why in many species very few workers attempt to reproduce and why immature females usually do not attempt to develop as queens rather than workers. Although our analyses are primarily focused on the social insects, our conclusions are likely to be general and to apply to other societies as well
Narrowband UVB phototherapy for clinically isolated syndrome: A trial to deliver the benefits of Vitamin D and other UVB-Induced molecules
Low vitamin D and insufficient sun exposure are additive independent risk factors for the development of multiple sclerosis (MS). The usual measure of vitamin D status, serum 25-hydroxy vitamin D [25(OH)D], is also a marker of recent exposure to the UVB rays of sunshine. The main evidence for a protective effect for MS development of higher 25(OH)D comes from observational studies, but this study design cannot separate out whether 25(OH)D is acting as a marker of vitamin D status, sun exposure, or both. In light of a lack of definitive outcomes in MS patients after trials of vitamin D supplementation and the ability of narrowband UVB to induce vitamin D, as well as other immune-regulatory molecules in skin, the Phototherapy for Clinically Isolated Syndrome (PhoCIS) trial was established to investigate the benefits of narrowband UVB, in addition to supplemented vitamin D, on MS development in individuals with Clinically Isolated Syndrome. We propose that the PhoCIS trial provides a fresh approach to re-defining the reported associations of 25(OH)D levels with MS development and progression
Changes in serum neurofilament light chain levels following narrowband ultraviolet B phototherapy in clinically isolated syndrome
Objective
To determine whether serum neurofilament light chain (sNfL) levels are suppressed in patients with the clinically isolated syndrome (CIS) following narrowband ultraviolet B phototherapy (UVB-PT).
Methods
sNfL levels were measured using a sensitive single-molecule array assay at baseline and up to 12 months in 17 patients with CIS, 10 of whom received UVB-PT, and were compared with healthy control (HC) and early relapsing remitting multiple sclerosis (RRMS) group. sNfL levels were correlated with magnetic resonance imaging total lesion volume (LV) determined using icobrain version 4.4.1 and with clinical outcomes.
Results
Baseline median sNfL levels were significantly higher in the CIS (20.6 pg/mL, interquartile range [IQR] 13.7â161.4) and RRMS groups (36.6 pg/ml [IQR] 16.2â212.2) than in HC (10.7 pg/ml [IQR] 4.9â21.5) (p = .012 and p = .0002, respectively), and were strongly correlated with T2 and T1 LV at 12 months (r = .800; p = .014 and r = .833; p = .008, respectively) in the CIS group. Analysis of changes in sNfL levels over time in the CIS group showed a significant cumulative suppressive effect of UVB-PT in the first 3 months (UVB-PT â10.6% vs non-UVB-PT +58.3%; p = .04) following which the levels in the two groups converged and continued to fall.
Conclusions
Our findings provide the basis for further studies to determine the utility of sNfL levels as a marker of neuro-axonal damage in CIS and early MS and for assessing the efficacy of new therapeutic interventions such as UVB-PT
Evolving Identification of Blood Cells Associated with Clinically Isolated Syndrome: Importance of Time since Clinical Presentation and Diagnostic MRI
It is not clear how the profile of immune cells in peripheral blood differs between patients with clinically isolated syndrome (CIS) and healthy controls (HC). This study aimed to identify a CIS peripheral blood signature that may provide clues for potential immunomodulatory approaches early in disease. Peripheral blood mononuclear cells (PBMCs) were collected from 18 people with CIS, 19 HC and 13 individuals with other demyelinating conditions (ODC) including multiple sclerosis (MS). Individuals with CIS separated into two groups, namely those with early (â€14 days post-diagnostic magnetic resonance imaging (MRI); n = 6) and late (â„27 days; n = 12) blood sampling. Transitional B cells were increased in the blood of CIS patients independently of when blood was taken. However, there were two time-dependent effects found in the late CIS group relative to HC, including decreased CD56bright NK cells, which correlated significantly with time since MRI, and increased CD141+ myeloid dendritic cell (mDC2) frequencies. Higher CD1c+ B cells and lower non-classical monocyte frequencies were characteristic of more recent demyelinating disease activity (ODC and early CIS). Analysing cell populations by time since symptoms (subjective) and diagnostic MRI (objective) may contribute to understanding CIS
IgG 3 + B cells are associated with the development of multiple sclerosis
Objectives
Diseaseâmodifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG3 antibodies and their uncharacterised Bâcell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG3+ B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically.
Methods
We designed a 31âparameter Bâcellâfocused mass cytometry panel to interrogate the role of peripheral blood IgG3+ B cells in MS progression of two different patient cohorts: one to investigate the Bâcell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of nonâMS controls.
Results
Nine distinct CD20+IgDâIgG3+ Bâcell subsets were identified. Significant changes in the proportion of CD21+CD24+CD27âCD38â and CD27+CD38hiCD71hi memory Bâcell subsets correlated with changes in serum IgG3 levels and time to conversion from CIS to MS. The same CD38â doubleânegative Bâcell subset was significantly elevated in MS patients with active forms of the disease. A third CD21+CD24+CD27+CD38â subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switchedâmemory Bâcell subset.
Conclusion
We have identified previously uncharacterised subsets of IgG3+ B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG3+ B cells to impact MS progression
Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome
Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1â4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to EpsteinâBarr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of âupstreamâ to âdownstreamâ IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS
Atomic and molecular suite of R-matrix codes for ultrafast dynamics in strong laser fields and electron/positron scattering
Synopsis: We describe and illustrate a number of recent developments of the atomic and molecular ab initio R-matrix suites for both time-dependent calculations of ultrafast laser-induced dynamics and time-independent calculations of photoionization and electron scattering
Recommended from our members
Atomic and molecular suite of R-matrix codes for ultrafast dynamics in strong laser fields and electron/positron scattering
We describe and illustrate a number of recent developments of the atomic and molecular ab initio R-matrix suites for both time-dependent calculations of ultrafast laser-induced dynamics and time-independentcalculations of photoionization and electron scattering. © 2019 Published under licence by IOP Publishing Ltd
Large-scale horizontal flows in the solar photosphere. IV. On the vertical structure of large-scale horizontal flows
In the recent papers, we introduced a method utilised to measure the flow
field. The method is based on the tracking of supergranular structures. We did
not precisely know, whether its results represent the flow field in the
photosphere or in some sub-photospheric layers. In this paper, in combination
with helioseismic data, we are able to estimate the depths in the solar
convection envelope, where the detected large-scale flow field is well
represented by the surface measurements. We got a clear answer to question what
kind of structures we track in full-disc Dopplergrams. It seems that in the
quiet Sun regions the supergranular structures are tracked, while in the
regions with the magnetic field the structures of the magnetic field are
dominant. This observation seems obvious, because the nature of Doppler
structures is different in the magnetic regions and in the quiet Sun. We show
that the large-scale flow detected by our method represents the motion of
plasma in layers down to ~10 Mm. The supergranules may therefore be treated as
the objects carried by the underlying large-scale velocity field.Comment: 8 pages, 5 figures, accepted in New Astronom
A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: The Treat-OA consortium
To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genomewide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81Ă10-5). The C allele conferred a reduced risk of 33% to 41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA
- âŠ