The SH2/SH3 Adaptor Protein Dock Interacts with the Ste20-like Kinase Misshapen in Controlling Growth Cone Motility

AbstractRecent studies suggest that the SH2/SH3 adaptor Dock/Nck transduces tyrosine phosphorylation signals to the actin cytoskeleton in regulating growth cone motility. The signaling cascade linking the action of Dock/Nck to the reorganization of cytoskeleton is poorly understood. We now demonstrate that Dock interacts with the Ste20-like kinase Misshapen (Msn) in the Drosophila photoreceptor (R cell) growth cones. Loss of msn causes a failure of growth cones to stop at the target, a phenotype similar to loss of dock, whereas overexpression of msn induces pretarget growth cone termination. Physical and genetic interactions between Msn and Dock indicate a role for Msn in the Dock signaling pathway. We propose that Msn functions as a key controller of growth cone cytoskeleton in response to Dock-mediated signals

Synergistic remineralization of enamel white spot lesions using mesoporous bioactive glasses loaded with amorphous calcium phosphate

Objectives: The purpose of this study was to create a new delivery system that can synergistically remineralize enamel white spot lesions (WSLs).Materials and methods: The delivery system (PAA-ACP@aMBG) was prepared by using aminated mesoporous bioactive glasses (aMBG) as the carrier loaded with polyacrylic-stabilized amorphous calcium phosphate (PAA-ACP). The materials were characterized by transmission electron microscopy (TEM), X-ray powder diffraction (XRD), inductively coupled plasma–optical emission spectrometry (ICP–OES), and so on. Forty-eight artificial WSLs enamel samples were randomized to four groups: artificial saliva (negative control, NC), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), PAA-ACP@aMBG, and MBG. The effects of demineralization and remineralization of the enamel surface were compared by means of surface microhardness (SMH) measurements, surface color change measurements, fluorescence microscopy (FM), X-ray diffraction (XRD) analysis and scanning electron microscopy (SEM).Results: There was no significant difference in the surface microhardness recovery rate (SMHRR) or color recovery rate (CRR) among the CPP-ACP group, PAA-ACP@aMBG group and MBG group (P>0.05), but these values were significantly higher than those in the NC group (p < 0.01). FM demonstrated that the remineralization depth in the PAA-ACP@aMBG group was significantly greater than that of the remaining three groups (p < 0.01). SEM analysis indicated that the enamel demineralization marks in the PAA-ACP@aMBG group, CPP-ACP group, and MBG group were obscured by mineral deposition.Conclusions: PAA-ACP@aMBG showed good mineralization properties, implying its great potential for clinical application

Quantitative trait locus mapping and candidate gene analysis for salt tolerance at bud stage in rice

Soil salinization has a serious influence on rice yield and quality. How to enhance salt tolerance in rice is a topical issue. In this study, 120 recombinant inbred line populations were generated through nonstop multi-generation selfing using a male indica rice variety Huazhan (Oryza sativa L. subsp. indica cv. ‘HZ’) and a female variety of Nekken2 (Oryza sativa L. subsp. japonica cv. ‘Nekken2’) as the parents. Germination under 80 mM NaCl conditions was measured and analyzed, and quantitative trait locus (QTL) mapping was completed using a genetic map. A total of 16 salt-tolerance QTL ranges were detected at bud stage in rice, which were situated on chromosomes 3, 4, 6, 8, 9, 10, 11, and 12. The maximum limit of detection was 4.69. Moreover, the qST12.3 was narrowed to a 192 kb region on chromosome 12 using map-based cloning strategy. Statistical analysis of the expression levels of these candidate genes under different NaCl concentrations by qRT-PCR revealed that qST12.3 (LOC_Os12g25200) was significantly down-regulated with increasing NaCl concentration, and the expression level of the chlorine-transporter-encoding gene LOC_Os12g25200 in HZ was significantly higher than that of Nekken2 under 0 mM NaCl. Sequencing analysis of LOC_Os12g25200 promoter region indicated that the gene expression difference between parents may be due to eight base differences in the promoter region. Through QTL mining and analysis, a plurality of candidate genes related to salt tolerance in rice was obtained, and the results showed that LOC_Os12g25200 might negatively regulate salt tolerance in rice. The results provide the basis for further screening and cultivation of salt-tolerant rice varieties and have laid the foundation for elucidating further molecular regulation mechanisms of salt tolerance in rice

Re-recognize early recurrence of persistent atrial fibrillation

AimsFew studies on early recurrence (ER) focused on patients with persistent atrial fibrillation (AF). We aimed to investigate the characteristics and clinical significance of ER in patients with persistent AF after catheter ablation (CA).MethodsA total of 348 consecutive patients who underwent first-time CA for persistent and long-standing persistent AF between January 2019 and May 2022 were investigated.ResultsAbout 5/348 (1.44%) patients who failed to convert to sinus rhythm after CA were excluded. A total of 110/343 (32.1%) patients had ER, in which 98 (89.1%) were persistent and 50.9% occurred in the first 24 h after CA. Compared with the patients without ER, those with ER were more likely to have late recurrence (LR) (92.7% vs. 1.7%, P < 0.001) during a median follow-up of 13 (IQR 6–23) months. ER was the most significant independent predictor for LR (OR 120.5, 95% CI 41.5–349.8, P < 0.001). ER as atrial flutter (AFL) had a lower risk of LR when compared with ER as AF (P = 0.011) and both AF and AFL (P = 0.003). Early intervention of the patient with ER improved the short-term outcomes (P < 0.001), not long-term outcomes. Only 22/251 (8.76%) patients of LR appears among those who had no recurrence in the first month.ConclusionsPatients with persistent AF may not have a blanking period but rather have a risk period. Clinical significance of the blanking period should be given differential treatment between paroxysmal AF and persistent AF

Giant intrinsic photoresponse in pristine graphene

When the Fermi level matches the Dirac point in graphene, the reduced charge screening can dramatically enhance electron-electron (e-e) scattering to produce a strongly interacting Dirac liquid. While the dominance of e-e scattering already leads to novel behaviors, such as electron hydrodynamic flow, further exotic phenomena have been predicted to arise specifically from the unique kinematics of e-e scattering in massless Dirac systems. Here, we use optoelectronic probes, which are highly sensitive to the kinematics of electron scattering, to uncover a giant intrinsic photocurrent response in pristine graphene. This photocurrent emerges exclusively at the charge neutrality point and vanishes abruptly at non-zero charge densities. Moreover, it is observed at places with broken reflection symmetry, and it is selectively enhanced at free graphene edges with sharp bends. Our findings reveal that the photocurrent relaxation is strongly suppressed by a drastic change of fast photocarrier kinematics in graphene when its Fermi level matches the Dirac point. The emergence of robust photocurrents in neutral Dirac materials promises new energy-harvesting functionalities and highlights intriguing electron dynamics in the optoelectronic response of Dirac fluids.Comment: Originally submitted versio

Growth of Large-Area and Highly Crystalline MoS2 Thin Layers on Insulating Substrates

The two-dimensional layer of molybdenum disulfide (MoS2) has recently attracted much interest due to its direct-gap property and potential applications in optoelectronics and energy harvesting. However, the synthetic approach to obtain high quality and large-area MoS2 atomic thin layers is still rare. Here we report that the high temperature annealing of a thermally decomposed ammonium thiomolybdate layer in the presence of sulfur can produce large-area MoS2 thin layers with superior electrical performance on insulating substrates. Spectroscopic and microscopic results reveal that the synthesized MoS2 sheets are highly crystalline. The electron mobility of the bottom-gate transistor devices made of the synthesized MoS2 layer is comparable with those of the micromechanically exfoliated thin sheets from MoS2 crystals. This synthetic approach is simple, scalable and applicable to other transition metal dichalcogenides. Meanwhile, the obtained MoS2 films are transferable to arbitrary substrates, providing great opportunities to make layered composites by stacking various atomically thin layers.Comment: manuscript submitted on 11-Dec-2011, revision submitted on 16-Feb-201

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival