Search

A method is proposed for analyzing fast (10 µs) single-molecule rotation trajectories in F1 adenosinetriphosphatase (F1-ATPase). This method is based on the distribution of jumps in the rotation angle that occur in the transitions during the steps between subsequent catalytic dwells. The method is complementary to the "stalling" technique devised by H. Noji et al. [Biophys. Rev. 9, 103-118, 2017], and can reveal multiple states not directly detectable as steps. A bimodal distribution of jumps is observed at certain angles, due to the system being in either of 2 states at the same rotation angle. In this method, a multistate theory is used that takes into account a viscoelastic fluctuation of the imaging probe. Using an established sequence of 3 specific states, a theoretical profile of angular jumps is predicted, without adjustable parameters, that agrees with experiment for most of the angular range. Agreement can be achieved at all angles by assuming a fourth state with an ~10 µs lifetime and a dwell angle about 40° after the adenosine 5'-triphosphate (ATP) binding dwell. The latter result suggests that the ATP binding in one β subunit and the adenosine 5'-diphosphate (ADP) release from another β subunit occur via a transient whose lifetime is ~10 µs and is about 6 orders of magnitude smaller than the lifetime for ADP release from a singly occupied F1-ATPase. An internal consistency test is given by comparing 2 independent ways of obtaining the relaxation time of the probe. They agree and are ~15 µs. [ABSTRACT FROM AUTHOR]

Aim To investigate whether aggressive periodontitis ( AgP) is associated with specific mt DNA polymorphisms or point mutations and furthermore whether mitochondrial dysfunction occurs in gingival fibroblasts of AgP patients. Materials and methods The mitochondrial DNA coding regions were amplified and sequenced in 22 overlapped fragments in 34 patients with AgP and 28 healthy controls for initial screening. We selected eleven SNPs for detailed investigation in the rest 30 AgP patients and 26 healthy controls, because all other variants occurred at relatively low frequencies or had no difference between two groups. Logistic regression models were used to analyze the association between mt DNA variants and AgP. Gingival fibroblasts were cultured from four patients with AgP and four healthy controls, and then mitochondrial membrane potential, reactive oxygen species production and cell proliferation were analyzed. Results Significant association was observed between aggressive periodontitis and eight mitochondrial polymorphisms: '8701A-9540T-10400C-10873T-14783T-15043G-15301G' ( OR = 3.471 (1.610-7.483), P = 0.001) and 10398A ( OR = 3.238 (1.481-7.078), P = 0.003). Compared with the controls, patients with aggressive periodontitis had a decrease in mitochondrial membrane potential and an increase in reactive oxygen species production. Conclusion In conclusion, we propose that mitochondrial dysfunction and '8701A-9540T-10400C-10873T-14783T-15043G-15301G, 10398A' are associated with and may increase the susceptibility to AgP in the Han Chinese population. [ABSTRACT FROM AUTHOR]

We revisit the transition from Alfv&Z#233;n resonance to forced magnetic reconnection with a focus on the property of their singularities. As the driven frequency tends to zero, the logarithmic singularity of Alfvén resonance shifts to the power-law singularity of forced reconnection, due to merging of the two resonance layers. The transition criterion depends on either kinetic effects or dissipations that resolve the singularity. As an example, a small but finite resistivity g is introduced to investigate the transition process. The transition threshold is then obtained as the driven frequency reaches a level of ~O((ζ/k)1/3). [ABSTRACT FROM AUTHOR]

Innate immunity plays an important role in psoriasis. The possible role of Toll-like receptors (TLRs) in the activation of innate immunity in psoriasis remains unknown. Serum antikeratin 16 (anti-K16) autoantibody levels are raised in patients with psoriasis. The aim of this study was to investigate the effects of anti-K16 antibodies on TLR2 and TLR4 expression in keratinocytes. Keratinocytes were incubated with mouse anti-K16 monoclonal antibodies. Levels of TLR2 and TLR4 were measured by quantitative real-time PCR and flow cytometry. TLR2 mRNA level was increased by 1.73-fold, 1.60-fold and 2.52-fold at 6, 24 and 36 h after incubation, respectively. TLR4 mRNA level was increased by 3.62-fold and 2.21-fold at 12 and 36 h, respectively. TLR2 protein expression was increased by 1.73-fold on the cell membrane and 2.22-fold in cell membrane and intracytoplasmic locations. There was no change in TLR4. The results of this study indicate that anti-K16 antibodies may be a modulator of TLRs. [ABSTRACT FROM AUTHOR]

A systematic numerical study is carried out, computing and comparing the plasma response to the resonant magnetic perturbation (RMP) field, applied for controlling edge localized modes (ELMs), in a series of tokamak plasmas with varying aspect ratio and utilizing the MARS-F code. The aspect ratio is scanned either by varying the plasma major radius at a fixed minor radius or by varying the latter while fixing the former. Both approaches yield similar results when compared in terms of quantities with proper normalizations. In general, a non-monotonic dependence of the resonant response field (normalized by the vacuum counterpart) near the plasma edge is found with varying aspect ratio, indicating that a given ELM control coil current configuration strongly favors plasmas with a certain aspect ratio. This optimal aspect ratio, on the other hand, depends on the toroidal as well as poloidal (i.e., coil phasing) spectra of the applied RMP field. The equilibrium (edge) safety factor, the plasma shape, and the plasma toroidal flow are all fixed to ensure that the effects identified here are predominantly due to the plasma aspect ratio. [ABSTRACT FROM AUTHOR]

Background The exact aetiology of vitiligo has not yet been established. Oxidative stress is involved in the pathophysiology of vitiligo. It has been described that some polymorphisms in the catalase (CAT) gene may affect the risk of vitiligo. However, the results were inconsistent. Objective We performed a meta-analysis of the published studies to derive a more precise estimate of the association between CAT T ⁄ C at codon 389 in exon 9 polymorphisms and vitiligo risk. Methods The PubMed, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI) databases were searched to identify relevant published studies. Results Four case–control studies (cases, 645; controls, 689) that investigated the association between C⁄ T polymorphisms of CAT exon 9 and the risk of vitiligo were retrieved and analysed. Our findings suggested a significant association between the CAT T ⁄ C exon 9 polymorphism and vitiligo risk (CT + TT vs. CC pooled odds ratio, 1.43; 95% confidence interval, 1.14–1.80; P = 0 .002). Conclusion We found a significant correlation between the CAT T ⁄C exon 9 polymorphism and the risk of vitiligo. [ABSTRACT FROM AUTHOR]

Vitamin D and its metabolites play an important role in calcium homeostasis, bone remodelling, hormone secretion, cell proliferation and differentiation. Recent studies also suggest a beneficial role of vitamin D in slowing the progression of tissue fibrosis. However, their effects on dermal fibrosis and keloids are unknown. To investigate the effect of 1,25-dihydroxyvitamin D3 (1,25D) in the pathogenesis of tissue fibrosis by keloid fibroblasts (KFs). KFs were cultured and exposed to different concentrations of 1,25D in the presence or absence of transforming growth factor (TGF)-β1. KF phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, immunofluorescence and multiplex enzyme-linked immunosorbent assay techniques. Collagen synthesis was evaluated by measuring H-proline incorporation. The effect of 1,25D on cell proliferation and viability was evaluated by Formazan assay, proliferating cell nuclear antigen expression and the colorimetric conversion of 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide. We confirmed the presence of vitamin D receptors (VDRs) in cultured keloid fibroblasts. Fibroblasts transfected with a vitamin D response element reporter construct and exposed to the active vitamin D metabolite 1,25D showed increased promoter activity indicating VDR functionality in these cells. Incubation of KFs with 1,25D suppressed TGF-β1-induced collagen type I, fibronectin and α-smooth muscle actin expression. 1,25D also modulated plasminogen activator inhibitor-1 and matrix metalloproteinase-9 expression induced by TGF-β1. Interestingly, 1,25D induced hepatocyte growth factor mRNA expression and protein secretion in keloid fibroblasts. This study highlights key mechanistic pathways through which vitamin D decreases fibrosis, and provides a rationale for studies to test vitamin D supplementation as a preventive and/or early treatment strategy for keloid and related fibrotic disorders. [ABSTRACT FROM AUTHOR]

A recently updated version of the MARS-F code [Y. Q. Liu et al., Phys. Plasmas 7, 3681 (2000); L. Li et al., Phys. Plasmas 25, 082512 (2018); and G. L. Xia et al., Nucl. Fusion 59, 126035 (2019)] is utilized to numerically investigate the plasma screening effect on the applied resonant magnetic perturbation (RMP) field, assuming various equilibrium flow models, including the toroidal flow, the parallel flow and their combinations, and poloidal and toroidal projections of the parallel flow. A parallel equilibrium flow with a uniform radial profile is found to have no effect on plasma screening of the RMP field. A sheared parallel flow, however, does change plasma screening. The poloidal projection of the parallel flow weakens plasma screening in the resistive-inertial regime. The effect on the favorable average curvature regime is found, however, to be non-monotonic. With the increasing flow speed, the poloidal projection first weakens Glasser-Green-Johnson (GGJ)-screening. Further increase in the flow speed results in enhanced GGJ-screening again. This non-monotonic behavior is related to the perturbed parallel shielding current, which appears also off the mode rational surface at fast flow due to additional resonances between the RMP perturbation and the sound wave continuum. These results indicate that flow induced plasma screening to the RMP field can have complicated characteristics, which, in turn, can have implications on the RMP field penetration into the plasma in experiments for controlling the edge localized modes. [ABSTRACT FROM AUTHOR]

A toroidal resistive magneto-hydrodynamic plasma response model, involving large magnetic islands, is proposed and numerically investigated, based on local flattening of the equilibrium pressure profile near a rational surface. It is assumed that such islands can be generated near the edge of the tokamak plasma, due to the penetration of the resonant magnetic perturbations, used for the purpose of controlling the edge localized mode. Within this model, it is found that the local flattening of the equilibrium pressure helps to mitigate the toroidal curvature induced screening effect [Glasser et al., Phys. Fluids 7, 875 (1975)]--the so called Glasser-Greene-Johnson screening, when the local toroidal flow near the mode rational surface is very slow (for example, as a result of mode locking associated with the field penetration). The saturation level of the plasma response amplitude is computed, as the plasma rotation frequency approaches zero. The local modification of the plasma resistivity inside the magnetic island is found to also affect the saturation level of the plasma response at vanishing flow. [ABSTRACT FROM AUTHOR]

Objectives Cognitive impairment is a common neurological problem in elderly people. In this study, we investigated whether tooth loss, periodontal parameters, and gene variations in the mitochondrial DNA displacement loop region are potential influencing factors on cognitive function. Design We employed a linear regression model to estimate cross-sectional association between number of teeth lost, periodontal parameters and Mini-mental State Examination score, adjusting for demographic factors, socioeconomic factors, general health status, smoking, drinking, and life habits. Participants A total of 905 Han Chinese people, ≥50 years of age, with complete data, were enrolled. Blood samples of 567 of the subjects were analyzed for correlation between mitochondrial DNA variants and Mini-mental State Examination score. Results The number of teeth lost ( β = −0.042, 95% CI: −0.061, −0.024, P < 0.001), two single nucleotide polymorphism ( SNP) points: A189G ( β = −1.540, 95% CI: −2.818, −0.263, P = 0.018) and A16164G ( β = −1.053, 95% CI: −2.054, −0.052, P = 0.039) in the mitochondrial DNA displacement loop region, and haplogroup Y ( β = −2.152, 95% CI: −4.062, −0.242, P = 0.027) were found to be negatively associated with Mini-mental State Examination scores in the fully adjusted model. No correlation was found between periodontal parameters and Mini-mental State Examination scores. Conclusion Number of teeth lost, mitochondrial SNPs, and haplogroup Y were correlated with cognitive function in this study population. [ABSTRACT FROM AUTHOR]

Background Generalised recalcitrant facial verruca plana responds poorly to current therapeutic options, including cryotherapy, topical drugs and carbon dioxide (CO2) laser. Case reports and uncontrolled studies suggested that topical photodynamic therapy (PDT) is effective choice of treatment free from potential complications associated with invasive therapies. Aims To investigate the efficacy and safety of PDT with different concentrations of photosensitiser in the treatment of verruca plana. Materials & Methods The two sides of a subject's face were separately randomized to receive aminolevulinic acid (ALA) of 5%, 10% or 20% concentration. All patients were irradiated with 633-nm red light for 339 J/cm2 total dose. Complete response (CR) rate was assessed on Week 4, 8, and 16 respectively. Results The mean overall clearance rate was 74.1%, 68.8%, and 64.6% on Week 4, 8, and 12, respectively, in the 110 treated sides. The CR rate was lower in the 5%-ALA group than in the 10%-ALA group (14.3% vs. 33.3%, p < 0.05) and 20%-ALA group (14.3% vs. 26.3%, p < 0.05) after 12 weeks. The mean severity of pain measured by visual analogue scale (VAS) scoring was 3.8 (range: 2 to 10, depending on the lesion location). The overall recurrence rate was 16.7% (4/24) on Week 12. Hyperpigmentation was observed in 61% (67/110) of all treated sides. On Week 4, 8, and 16, hyperpigmentation was more developed in the 20%-ALA group than in the other two groups ( p < 0.05). Discussion In terms of complete clearance rate, the 5% ALA-PDT group was significantly inferior to the 10% and 20% ALA-PDT groups at each follow-up. In contrast, the 20% ALA group showed a higher incidence rate of transient hyperpigmentation than the other two groups. Conclusions This randomised clinical trial suggests that PDT with ALA of 10% concentration offers better efficacy and safety than 5% or 20% concentration for generalised recalcitrant facial verruca plana. [ABSTRACT FROM AUTHOR]

Background The association between trauma and melanoma has been a controversial issue. Objectives To analyse the profiles of melanoma, and to determine whether trauma is associated with development of acral melanoma in the Chinese population. Patients and Methods Retrospective analysis of 685 cases of cutaneous melanoma in the dermatology departments of Xijing Hospital in northwestern China and Xinan Hospital in southwestern China from 1982 to 2011. Results Of the 685 patients included in the study, 437 (63.8%) suffered from melanoma on the extremities. A total of 104 patients (15.2%) exhibited an association between trauma and melanoma. The primary anatomic sites of the tumours were the upper extremities (17, 16.3%), lower extremities (74, 71.2%) and other sites (13, 12.5%). Among these cases, the extremities were with remarkably higher risks of post-trauma melanoma than the other sites [adjusted odds ratio ( OR) 3.968; 95% confidence interval ( CI) 2.267-5.592]. Notably, patients in the south part of China were with a stronger risk of post-trauma melanoma on the lower extremities than those in the north (adjusted OR 1.764; 95% CI 1.192-2.666) part. In addition, a significant higher risk of post-trauma melanoma on the extremities was observed in the male gender (adjusted OR 1.848; 95% CI 1.186-2.887). Conclusions Our findings provide epidemiological evidence for a potential association between traumatic events and melanoma of the extremities, especially the lower limbs, where a history of trauma is more likely. [ABSTRACT FROM AUTHOR]

As part of the Tibet Ozone, Aerosol and Radiation (TOAR) project, a micropulse lidar was operated in Naqu (31.5°N, 92.1°E; 4508 m MSL) on the Tibetan Plateau to observe cirrus clouds continuously from 19 July to 26 August 2011. During the experiment, the time coverage of ice clouds only was 15% in the upper troposphere (above 9.5 km MSL). The cirrus top/bottom altitudes (mean values of 15.6/14.7 km) are comparable to those measured previously at tropical sites but relatively higher than those measured at midlatitude sites. The majority of the cloud layers yielded a lidar ratio between 10 and 40 sr, with a mean value of 28 ± 15 sr, characterized by a bimodal frequency distribution. Subvisible, thin, and opaque cirrus formation was observed in 16%, 34%, and 50% of all cirrus cases, respectively. A mean cirrus optical depth of 0.33 was observed over the Tibetan Plateau, slightly higher than those in the subtropics and tropics. With decreasing temperature, the lidar ratio increased slightly, whereas the mean extinction coefficient decreased significantly. The occurrence of clouds is highly correlated with the outgoing longwave radiation and the strong cold perturbations in the upper troposphere. Deep convective activity and Rossby waves are important dynamical processes that control cirrus variations over the Tibetan Plateau, where both anvil cirrus outflowing from convective cumulonimbus clouds and large-scale strong cold perturbations in the upper troposphere should play an important role in cirrus formation. [ABSTRACT FROM AUTHOR]

Disturbances in GABAergic system have been observed in schizophrenics.1,2,3 In the present study, population association analysis was performed on 19 SNPs in the a1, ß2, ?2, ? and p subunit genes of GABAA receptor. Five SNPs in GABRB2, namely B2I7G1584T, rs1816071, rs194072, rs252944 and rs187269, were found to be significantly associated, and their haplotypes in linkage disequilibrium, with schizophrenia. This represents the first report on any disease association of SNPs in the human GABAA receptor genes, and focuses attention on the GABAergic hypothesis of schizophrenia etiology.3,4Molecular Psychiatry (2004) 9, 603-608. doi:10.1038/sj.mp.4001461 Published online 16 December 2003 [ABSTRACT FROM AUTHOR]