Since 1995, more than 500 exoplanets have been detected using different techniques, of which 12 were detected with gravitational microlensing. Most of these are gravitationally bound to their host ...stars. There is some evidence of free-floating planetary-mass objects in young star-forming regions, but these objects are limited to massive objects of 3 to 15 Jupiter masses with large uncertainties in photometric mass estimates and their abundance. Here, we report the discovery of a population of unbound or distant Jupiter-mass objects, which are almost twice (1.8(+1.7)(-0.8)) as common as main-sequence stars, based on two years of gravitational microlensing survey observations towards the Galactic Bulge. These planetary-mass objects have no host stars that can be detected within about ten astronomical units by gravitational microlensing. However, a comparison with constraints from direct imaging suggests that most of these planetary-mass objects are not bound to any host star. An abrupt change in the mass function at about one Jupiter mass favours the idea that their formation process is different from that of stars and brown dwarfs. They may have formed in proto-planetary disks and subsequently scattered into unbound or very distant orbits.
Full text
Available for:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite the significant impact of clonal hematopoiesis (CH) on leukemogenesis, the pathogenesis of CH is still not fully understood.
Utilizing a novel single-cell sequencing platform that allows for ...simultaneous detection of mutations and gene expression, we examined the gene expression profiles of hematopoietic stem and progenitor cells (HSPCs) harboring CH-related mutations from CH(+) cases, which was compared with that of wild-type (WT) cells from both CH(+) and CH(−) cases. Age-related changes in the bone marrow (BM) environment were also assessed using CH(−) cases.
In 12 patients with CH, genes associated with cell proliferation were upregulated in mutant cells. Significantly, mutant cells showed decreased expression of genes related to inflammatory responses, which were enhanced in BM cells from aged CH(−) cases, indicating the potential contribution of aged BM environment to the positive selection of mutant cells. Unexpectedly, WT cells from 3 TET2-CH(+) cases demonstrated significant upregulation of genes related to interferon response and cell proliferation, compared with those from age-matched CH(−) cases, suggesting the altered BM environments. Notably, when competitively transplanted with Tet2-knockout (KO) cells, WT HSPCs displayed enhanced expression of genes associated with cell proliferation and interferon signalling, compared with those transplanted with WT cells, implying non-cell autonomous effects of mutant cells.
These results suggest that mutant cells in CH(+) BM may exert non-cell autonomous effects on WT cells. Alongside aged BM environments, these effects may contribute to the positive selection of CH clones, playing a pivotal role in the pathogenesis of CH.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
: We determined the autoantibody profile in autoimmune thyroid diseases (AITD) and examined the distribution of thyroid-related autoantibodies in other autoimmune disorders.
Methods
: We ...tested sera from 234 patients with Graves’ disease (GD), 130 with Hashimoto’s thyroiditis (HT), 249 with other autoimmune diseases, and 50 healthy controls by enzyme-linked immunosorbent assay or radioimmunoassay.
Results
: Autoantibodies except TSH receptor antibody (Ab), anti-thyroglobulin (Tg) Ab and anti-thyroid peroxidase (TPO) Ab were not significantly prevalent in patients with AITD despite a significantly high elevation of thyroid-related Ab. Significant prevalence of autoantibodies related to AITD was observed in type 1 diabetes patients. Elevation of anti-Tg Ab was seen in patients with primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH), and anti-TPO Ab was elevated in patients with PBC. Although the prevalence of anti-acetyl-choline receptor Ab and systemic lupus erythematosus (SLE)-related Ab was significant in AIH, primary Sjögren’s syndrome (pSS)-related Ab were also found in both liver diseases. In
myasthenia gravis
(MG) patients, thyroid-related Ab and pSS-related Ab were detected in both MG groups, although SLE-related Ab were limited to the anti-muscle specific kinase Ab-positive MG patients. In patients with connective tissue diseases, anti-Tg Ab and anti-TPO Ab were significantly prevalent.
Conclusion
: Thyroid-related Ab were significantly elevated in all autoimmune diseases. Conversely, the elevations of Ab were not significant in the patients with AITD, suggesting a close relationship between AITD and other immune-mediated diseases.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and purpose
The differences in the characteristics of thymus histology, coexisting autoimmune diseases and related autoantibodies between anti‐muscle‐specific receptor tyrosine kinase ...(MuSK)‐antibody (Ab)‐positive myasthenia gravis (MG) patients, and anti‐acetylcholine receptor (AChR)‐Ab‐positive MG patients are not clearly defined.
Methods
The types of thymus histology, coexisting autoimmune diseases and associated Abs in 83 MuSK‐Ab‐positive patients nationwide were investigated and were compared with those in AChR‐Ab‐positive patients followed at our institute (n = 83). As for the autoantibodies associated with thymoma, titin Abs were measured.
Results
Thymoma was not present in any of the MuSK‐Ab‐positive patients but presented in 21 patients (25.3%) amongst the AChR‐Ab‐positive patients. Titin Abs were absent in MuSK‐Ab‐positive patients but positive in 25 (30.1%) of the AChR‐Ab‐positive patients. Concomitant autoimmune diseases were present in eight MuSK‐Ab‐positive patients (9.6%) amongst whom Hashimoto's thyroiditis and rheumatoid arthritis predominated, whereas 22 AChR‐Ab‐positive patients (26.5%) had one or more concomitant autoimmune diseases of which Graves' disease predominated.
Conclusions
Differences in frequency of thymoma and thymic hyperplasia, coexisting autoimmune diseases and autoantibody positivity between MuSK‐Ab‐positive and AChR‐Ab‐positive MG were indicated, suggesting that, in contrast with AChR‐Ab‐positive MG, thymus does not seem to be involved in the pathogenic mechanisms of MuSK‐Ab‐positive MG.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Lambert–Eaton myasthenic syndrome (LEMS), often associated with small‐cell lung carcinoma (SCLC), is a disorder of acetylcholine (ACh) release from motor nerve terminals. In most patients, it is ...caused by autoantibodies against the P/Q‐type voltage‐gated calcium channels (VGCC) that trigger ACh release. However, these antibodies are not detected in approximately 15% of clinically and electrophysiologically typical cases. The M1‐type pre‐synaptic muscarinic ACh receptor (M1 mAChR) modulates cholinergic neuromuscular transmission by linking to P/Q‐type VGCC, and may partially compensate for the reduced calcium entry. Immunoblotting against solubilized human M1 mAChR, we detected autoantibodies in: (a) 14 of 20 (70%) anti‐VGCC‐positive LEMS patients; (b) all five anti‐VGCC‐negative LEMS patients, one of whose serum had previously passively transferred LEMS‐type electrophysiological defects to mice; (c) all five LEMS patients with autonomic symptoms; (d) seven of 25 (28%) myasthenia gravis (MG) patients in whom increased ACh release partially compensates for post‐synaptic defects; (e) none of 10 SCLC patients without LEMS. Although not proving primary pathogenicity of anti‐M1 mAChR antibodies, the present results highlight their potential to affect synaptic compensatory mechanisms, more in LEMS than MG.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Anti-ryanodine receptor (RyR) antibodies were measured in sera from 33 myasthenia gravis (MG) patients using three peptides from the human RyR1 sequence, two C-terminal peptides included in the ...functional calcium release channel, and an N-terminal peptide implicated in ion-conduction. Antibodies were more frequently positive against the two C-terminal peptides, particularly in thymoma-associated MG. In a preliminary open trial with FK506, immunosuppressant and enhancer of RyR-related sarcoplasmic calcium release, the authors observed the sustained benefits in anti-RyR-positive MG patients.
PDF
