Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may ...contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant‐expressed miRNAs using real‐time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant‐expressed miRNAs was detected using real‐time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR‐145, miR‐224, miR‐513‐5p, miR‐150, miR‐516a‐5p, miR‐483‐5p and miR‐629, were found to be potentially abnormally expressed in SLE T cells. After validation, under‐expressed miR‐145 and over‐expressed miR‐224 were noted. We further found that STAT1 mRNA targeted by miR‐145 was over‐expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR‐224 was under‐expressed in SLE T cells. Transfection of Jurkat cells with miR‐145 suppressed STAT1 and miR‐224 transfection suppressed API5 protein expression. Over‐expression of miR‐224 facilitates activation‐induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR‐145 and miR‐224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation‐induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription‐1 (STAT)‐1 expression in patients with SLE.
Peatlands contain a large belowground carbon (C) stock in the biosphere, and their dynamics have important implications for the global carbon cycle. However, there are still large uncertainties in C ...stock estimates and poor understanding of C dynamics across timescales. Here I review different approaches and associated uncertainties of C stock estimates in the literature, and on the basis of the literature review my best estimate of C stocks and uncertainty is 500 ± 100 (approximate range) gigatons of C (Gt C) in northern peatlands. The greatest source of uncertainty for all the approaches is the lack or insufficient representation of data, including depth, bulk density and carbon accumulation data, especially from the world's large peatlands. Several ways to improve estimates of peat carbon stocks are also discussed in this paper, including the estimates of C stocks by regions and further utilizations of widely available basal peat ages. Changes in peatland carbon stocks over time, estimated using Sphagnum (peat moss) spore data and down-core peat accumulation records, show different patterns during the Holocene, and I argue that spore-based approach underestimates the abundance of peatlands in their early histories. Considering long-term peat decomposition using peat accumulation data allows estimates of net carbon sequestration rates by peatlands, or net (ecosystem) carbon balance (NECB), which indicates more than half of peat carbon (> 270 Gt C) was sequestrated before 7000 yr ago during the Holocene. Contemporary carbon flux studies at 5 peatland sites show much larger NECB during the last decade (32 ± 7.8 (S.E.) g C m−2 yr–1) than during the last 7000 yr (∼ 11 g C m−2 yr–1), as modeled from peat records across northern peatlands. This discrepancy highlights the urgent need for carbon accumulation data and process understanding, especially at decadal and centennial timescales, that would bridge current knowledge gaps and facilitate comparisons of NECB across all timescales.
Summary
We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T ...cells from the first five RA patients and five controls were analysed by real‐time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR‐223 and miR‐34b were over‐expressed in RA T cells. The expression levels of miR‐223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR‐223 mimic suppressed insulin‐like growth factor‐1 receptor (IGF‐1R) and transfection with miR‐34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF‐1R but not CREB was decreased in RA T cells. The addition of recombinant IGF‐1‐stimulated interleukin (IL)‐10 production by activated normal T cells, but not RA T cells. The transfection of miR‐223 mimic impaired IGF‐1‐mediated IL‐10 production in activated normal T cells. The expression levels of SCD5, targeted by miR‐34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR‐223 and miR‐34b were over‐expressed in RA T cells, but only the miR‐223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR‐223 expression could impair the IGF‐1‐mediated IL‐10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti‐inflammatory cytokines.
Objective
Human complement C4 is complex, with multiple layers of diversity. The aims of this study were to elucidate the copy number variations (CNVs) of C4A and C4B in relation to disease risk in ...systemic lupus erythematosus (SLE), and to compare the basis of race‐specific C4A deficiency between East Asians and individuals of European descent.
Methods
The East Asian study population included 999 SLE patients and 1,347 healthy subjects. Variations in gene copy numbers (GCNs) of total C4, C4A, and C4B, as well as C4‐Long and C4‐Short genes, were determined and validated using independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein occurring concurrently with C4A deficiency.
Results
In East Asians, high GCNs of total C4 and C4A were strongly protective against SLE, whereas low and medium GCNs of total C4 and C4A, and the absence of C4‐Short genes, were risk factors for SLE. Homozygous C4A deficiency was infrequent in East Asian subjects, but had an odds ratio (OR) of 12.4 (P = 0.0015) for SLE disease susceptibility. Low serum complement levels were strongly associated with low GCNs of total C4 (OR 3.19, P = 7.3 × 10−7) and C4B (OR 2.53, P = 2.5 × 10−5). Patients with low serum complement levels had high frequencies of anti–double‐stranded DNA antibodies (OR 4.96, P = 9.7 × 10−17), hemolytic anemia (OR 3.89, P = 3.6 × 10−10), and renal disease (OR 2.18, P = 8.5 × 10−6). The monomodular‐Short haplotype found to be prevalent in European Americans with C4A deficiency, which was in linkage disequilibrium with HLA–DRB1*0301, was scarce in East Asians. Instead, most East Asian subjects with C4A deficiency were found to have a recombinant haplotype with bimodular C4‐Long and C4‐Short genes, encoding C4B1 and C4B96, which was linked to HLA–DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96.
Conclusion
C4 CNVs and deficiency of C4A both play an important role in the risk and manifestations of SLE in East Asian and European populations.
Semiconductor InSb nanowires are expected to provide an excellent material platform for the study of Majorana fermions in solid state systems. Here, we report on the realization of a Nb–InSb ...nanowire–Nb hybrid quantum device and the observation of a zero-bias conductance peak structure in the device. An InSb nanowire quantum dot is formed in the device between the two Nb contacts. Due to the proximity effect, the InSb nanowire segments covered by the superconductor Nb contacts turn to superconductors with a superconducting energy gap Δ InSb ∼ 0.25 meV. A tunable critical supercurrent is observed in the device in high back gate voltage regions in which the Fermi level in the InSb nanowire is located above the tunneling barriers of the quantum dot and the device is open to conduction. When a perpendicular magnetic field is applied to the devices, the critical supercurrent is seen to decrease as the magnetic field increases. However, at sufficiently low back gate voltages, the device shows the quasi-particle Coulomb blockade characteristics and the supercurrent is strongly suppressed even at zero magnetic field. This transport characteristic changes when a perpendicular magnetic field stronger than a critical value, at which the Zeeman energy in the InSb nanowire is E z ∼ Δ InSb , is applied to the device. In this case, the transport measurements show a conductance peak at the zero bias voltage and the entire InSb nanowire in the device behaves as in a topological superconductor phase. We also show that this zero-bias conductance peak structure can persist over a large range of applied magnetic fields and could be interpreted as a transport signature of Majorana fermions in the InSb nanowire.
Summary
Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved ...in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real‐time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR‐16, miR‐221 and let‐7i were over‐expressed in AS T cells and the expression of miR‐221 and let‐7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR‐16, miR‐221 and let‐7i were measured by Western blotting. We found that the protein levels of Toll‐like receptor‐4 (TLR‐4), a target of let‐7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)‐γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR‐4 agonist, inhibited IFN‐γ secretion by anti‐CD3+anti‐CD28 antibodies‐stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let‐7i enhanced IFN‐γ production by anti‐CD3+anti‐CD28+ lipopolysaccharide (LPS)‐stimulated normal T cells. In contrast, the decreased expression of let‐7i suppressed IFN‐γ production by anti‐CD3+anti‐CD28+ LPS‐stimulated AS T cells. In conclusion, we found that miR‐16, miR‐221 and let‐7i were over‐expressed in AS T cells, but only miR‐221 and let‐7i were associated with BASRI of lumbar spine. In the functional studies, the increased let‐7i expression facilitated the T helper type 1 (IFN‐γ) immune response in T cells.
We report dissipative magnon-photon coupling caused by the cavity Lenz effect, where the magnons in a magnet induce a rf current in the cavity, leading to a cavity backaction that impedes the ...magnetization dynamics. This effect is revealed in our experiment as level attraction with a coalescence of hybridized magnon-photon modes, which is distinctly different from level repulsion with mode anticrossing caused by coherent magnon-photon coupling. We develop a method to control the interpolation of coherent and dissipative magnon-photon coupling, and observe a matching condition where the two effects cancel. Our work sheds light on the so-far hidden side of magnon-photon coupling, opening a new avenue for controlling and utilizing light-matter interactions.
The present case-control study was to investigate the relationships of plasma leptin level and anthropometric measures of adiposity with the risk of breast cancer. Questionnaire information, ...anthropometric measures and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei, between 2004 and 2006. Plasma levels of leptin were measured by RIA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the associations. Overall, higher leptin concentrations were significantly associated with an increased risk of breast cancer (OR (95% CI) for top vs bottom tertile of leptin was 1.63 (1.07-2.49), P(trend)=0.009). Waist circumference was a significant anthropometric factor for breast cancer in both pre- and postmenopausal women. Furthermore, the associations of leptin with breast cancer risk remained after adjustment for obesity indices. These results suggest that leptin may have an independent role in breast tumorigenesis. Regardless of the impact of circulating leptin, more research is needed to elucidate molecular mechanisms and local leptin levels that are critical for the development of breast cancers.
Illuminating gravitational waves Kasliwal, M. M.; Nakar, E.; Singer, L. P. ...
Science,
12/2017, Volume:
358, Issue:
6370
Journal Article
Peer reviewed
Open access
Merging neutron stars offer an excellent laboratory for simultaneously studying strong-field gravity and matter in extreme environments. We establish the physical association of an electromagnetic ...counterpart (EM170817) with gravitational waves (GW170817) detected from merging neutron stars. By synthesizing a panchromatic data set, we demonstrate that merging neutron stars are a long-sought production site forging heavy elements by r-process nucleosynthesis. The weak gamma rays seen in EM170817 are dissimilar to classical short gamma-ray bursts with ultrarelativistic jets. Instead, we suggest that breakout of a wide-angle, mildly relativistic cocoon engulfing the jet explains the low-luminosity gamma rays, the high-luminosity ultraviolet-optical-infrared, and the delayed radio and x-ray emission. We posit that all neutron star mergers may lead to a wide-angle cocoon breakout, sometimes accompanied by a successful jet and sometimes by a choked jet.
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