The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has ...been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined.
A single 15 min session of forced swimming increased P-Erk2 levels 2-3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2-5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to approximately 300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas.
Swim stress specifically and markedly enhanced the phosphorylation of the MAPKKs P-MEK1/2 and P-MKK4 in all brain regions tested without apparent alteration in the phosphorylation of P-MKK3/6. Curiously, phosphorylation of their cognate substrates (Erk and JNK) was increased to a much more modest extent, and in some brain regions was not altered. Similarly, there was a region-specific discrepancy between Erk and CREB phosphorylation. Possible explanations for these findings and comparison with the effects of restraint stress will be discussed.
Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only ...one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10. Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22–0.24 lower compared to fully structured interviews and 0.06–0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82–0.92) and 0.86 (0.82–0.88). Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.
Modern storage systems adopt erasure coding to maintain fault tolerance with low storage redundancy. However, how to improve the performance of degraded reads in erasure-coded storage has been a ...critical issue. We revisit this problem from two different perspectives that are neglected by existing studies: data placement and encoding rules. To this end, we propose encoding-aware data placement (EDP), which mitigates the number of I/Os in degraded reads during a single failure for general XOR-based erasure codes. EDP carefully selects appropriate parity units to be generated by sequential data based on the encoding rules and establishes their generation orders. We further refine the data placement for optimizing the degraded reads to any two sequential data units. Trace-driven evaluation results show that EDP significantly reduces I/Os in degraded reads and hence shortens the read time.
Dental caries is associated with plaque dysbiosis, leading to an increase in the proportions of acidogenic and aciduric bacteria at the expense of alkali-generating commensal species. Stannous ...fluoride (SnF2) slows the progression of caries by remineralization of early lesions but has also been suggested to inhibit glycolysis of aciduric bacteria. Casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) promotes fluoride remineralization by acting as a salivary biomimetic that releases bioavailable calcium and phosphate ions, and the peptide complex has also been suggested to modify plaque composition. We developed a polymicrobial biofilm model of caries using 6 bacterial species representative of supragingival plaque that were cultured on sound human enamel and pulsed with sucrose 4 times a day to produce a high cariogenic challenge. We used this model to explore the mechanisms of action of SnF2 and CPP-ACP. Bacterial species in the biofilms were enumerated with 16S rRNA gene sequence analyses, and mineral loss and lesion formation were determined in the enamel directly under the polymicrobial biofilms via transverse microradiography. The model tested the twice-daily addition of SnF2, CPP-ACP, or both. SnF2 treatment reduced demineralization by 50% and had a slight effect on the composition of the polymicrobial biofilm. CPP-ACP treatment caused a similar inhibition of enamel demineralization (50%), a decrease in Actinomyces naeslundii and Lactobacillus casei abundance, and an increase in Streptococcus sanguinis and Fusobacterium nucleatum abundance in the polymicrobial biofilm. A combination of SnF2 and CPP-ACP resulted in a greater suppression of the acidogenic and aciduric bacteria and a significant 72% inhibition of enamel demineralization.
We studied the feasibility of observing light-by-light scattering in a photon–photon collider based on an existing accelerator complex and a commercially available laser system. We investigated the ...statistical significance of the signal over the QED backgrounds through a Monte Carlo simulation with a detector model. The study showed that light-by-light scattering can be observed with a statistical significance of eight to ten sigma in a year of operation, depending on the operating conditions.
Physical and electrochemical phenomena at the surfaces of transition metal oxides and their coupling to local functionality remains one of the enigmas of condensed matter physics. Understanding the ...emergent physical phenomena at surfaces requires the capability to probe the local composition, map order parameter fields and establish their coupling to electronic properties. Here we demonstrate that measuring the sub-30-pm displacements of atoms from high-symmetry positions in the atomically resolved scanning tunnelling microscopy allows the physical order parameter fields to be visualized in real space on the single-atom level. Here, this local crystallographic analysis is applied to the in-situ-grown manganite surfaces. In particular, using direct bond-angle mapping we report direct observation of structural domains on manganite surfaces, and trace their origin to surface-chemistry-induced stabilization of ordered Jahn-Teller displacements. Density functional calculations provide insight into the intriguing interplay between the various degrees of freedom now resolved on the atomic level.
The Double Star mission Liu, Z. X.; Escoubet, C. P; Pu, Z. ...
Annales geophysicae (1988),
11/2005, Letnik:
23, Številka:
8
Journal Article
Recenzirano
Odprti dostop
The Double Star Programme (DSP) was first proposed by China in March, 1997 at the Fragrant Hill Workshop on Space Science, Beijing, organized by the Chinese Academy of Science. It is the first ...mission in collaboration between China and ESA. The mission is made of two spacecraft to investigate the magnetospheric global processes and their response to the interplanetary disturbances in conjunction with the Cluster mission. The first spacecraft, TC-1 (Tan Ce means "Explorer"), was launched on 29 December 2003, and the second one, TC-2, on 25 July 2004 on board two Chinese Long March 2C rockets. TC-1 was injected in an equatorial orbit of 570x79000 km altitude with a 28° inclination and TC-2 in a polar orbit of 560x38000 km altitude. The orbits have been designed to complement the Cluster mission by maximizing the time when both Cluster and Double Star are in the same scientific regions. The two missions allow simultaneous observations of the Earth magnetosphere from six points in space. To facilitate the comparison of data, half of the Double Star payload is made of spare or duplicates of the Cluster instruments; the other half is made of Chinese instruments. The science operations are coordinated by the Chinese DSP Scientific Operations Centre (DSOC) in Beijing and the European Payload Operations Service (EPOS) at RAL, UK. The spacecraft and ground segment operations are performed by the DSP Operations and Management Centre (DOMC) and DSOC in China, using three ground station, in Beijing, Shanghai and Villafranca.
Abstract
Dental caries, erosion and hypersensitivity are major public health problems. SnF
2
is used widely in oral care products to help prevent/treat these conditions. Casein ...phosphopeptide-stabilised amorphous calcium phosphate nanocomplexes (CPP-ACP) are a biomimetic nanotechnology of salivary phosphopeptide-ACP complexes that deliver bioavailable calcium and phosphate ions to promote dental remineralisation (repair). We show here using
in vitro
studies and a double-blind, randomised controlled, cross-over design
in situ
clinical trial that SnF
2
and CPP-ACP interact to form a nanofilament coating on the tooth surface and that together they are superior in their ability to promote dental remineralisation. Sn(II) by cross-linking the CPP-ACP helps to stabilise the complexes which improves delivery to the tooth surface and enhances binding and ion incorporation into tooth mineral. The combination of SnF
2
and CPP-ACP in oral care products may significantly improve their efficacy in prevention/treatment of dental caries/erosion and hypersensitivity.
Permanent-magnet flux-switching (PMFS) machine offers high torque density, impressive flux-weakening capability and mechanical ruggedness because of its distinctive configuration, and is potentially ...suitable for the application in automotive integrated-starter-generators (ISGs). However, the PMFS machine generally exhibits higher cogging torque compared with other machines commonly used in ISGs. Therefore, the minimisation of the cogging torque in the PMFS machine for its utility in ISGs is of particular importance. Four rotor topologies are proposed in this paper as cost-effective means to suppress the cogging torque of a PMFS ISG. The validity of the proposed techniques has been confirmed by both two-dimensional finite-element analysis and experimental results. Moreover, the influence on the back electromagnetic force by these techniques is also investigated.
Aims
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are ...limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism.
Methods
Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.
Results
Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments.
Conclusion
Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513.
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