The influence of induced moods on aging of phonological encoding in spoken word production: an ERP study

This study investigated the influence of induced mood on the phonological encoding involved in Chinese spoken word production with a picture-word inference task while concurrently recorded electrophysiological signals. In the experiment, young and older participants watched videos for inducing positive, negative, or neutral mood, and then they were instructed to name target picture while ignoring phonologically related or unrelated distractor words. A phonological facilitation effect was observed in young adults but not in older adults, suggesting an age-related decline of phonological encoding. Both groups showed an inhibition effect in negative mood but not in positive mood, suggesting that speakers have different processing styles in different moods. ERP data revealed a phonological effect around the time window of 250–350 ms in both groups. Meanwhile, young adults showed a phonological effect around 350–450 ms in negative mood and positive mood which may reflect self-monitoring in speech production. We suggest that the former effect may reflect phonological encoding while the latter reflects self-monitoring of internal syllables or phonemes. Furthermore, induced moods influence the phonological effect in older and young adults differently. Behavioral and ERP results provide consistent evidence for the aging decline of phonological encoding in spoken word production

Preoperative levels of folate receptor-positive circulating tumor cells in different subtypes of early-stage lung adenocarcinoma: Predictive value for determining extent of surgical resection

BackgroundThe objective was to measure the correlations of preoperative levels of folate receptor-positive circulating tumor cells (FR+CTCs) with clinical characteristics and histologic subtype in early-stage lung adenocarcinoma, and to determine the predictive value of FR+CTC level in preoperative determination of the extent of surgical resection.Patients and methodsIn this retrospective, single-institution, observational study, preoperative FR+CTC levels were measured via ligand-targeted enzyme-linked polymerization in patients with early-stage lung adenocarcinoma. Receiver operating characteristic (ROC) analysis was used to identify the optimal cutoff value of FR+CTC level for prediction of various clinical characteristics and histologic subtypes.ResultsNo significant difference in FR+CTC level was observed among patients with adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) (P = 0.813). Within the non-mucinous adenocarcinoma group, no difference was observed among patients with tumors whose predominant growth patterns were lepidic, acinar, papillary, micropapillary, solid, and complex gland (P = 0.053). However, significant differences in FR+CTC level were observed between patients with and without the micropapillary subtype [11.21 (8.22-13.61) vs. 9.85 (7.43-12.63), P = 0.017], between those with and without the solid subtype [12.16 (8.27-14.90) vs. 9.87 (7.50-12.49), P = 0.022], and between those with any of the advanced subtypes (micropapillary, solid, or complex glands) vs. none of these [10.48 (7.83-13.67) vs. 9.76 (7.42-12.42), P = 0.032]. FR+CTC level was also correlated with degree of differentiation of lung adenocarcinoma (P = 0.033), presence of visceral pleural invasion (VPI) of lung carcinoma (P = 0.003), and lymph node metastasis of lung carcinoma (P = 0.035).ConclusionFR+CTC level is of potential predictive value in determining the presence of aggressive histologic patterns (micropapillary, solid, and advanced subtypes), degree of differentiation, and occurrence of VPI and lymph node metastasis in IAC. Measurement of FR+CTC level combined with intraoperative frozen sections may represent a more effective method of guiding resection strategy in cases of cT1N0M0 IAC with high-risk factors

Choroidal thickness and vascular microstructure parameters in Chinese school-age children with high hyperopia using optical coherence tomography

BackgroundThe current study was to evaluate the choroidal thickness (CT) and vascular microstructure parameters in Chinese children with high hyperopia through enhanced depth imaging optical coherence tomography (EDI-OCT).MethodsCross-sectional study. A total of 23 children with high hyperopia and 29 children with normal refractive status were retrospectively enrolled in the study. The measurement of the macular CT, 7 points: the sub-foveal area point, the temporal and nasal points at a radius of 0.5-mm, 1.5-mm, and 3-mm were measured. After binarization of the OCT images, the total choroidal area (TCA), stromal area (SA) as well as the luminal area (LA) were identified and measured. The choroidal vascularity index (CVI) was defined as the ratio of LA to TCA. The independent t-test for normal distributions and Kruskal-Wallis tests for non-normal distributions were used to compare other parameters between groups. The Tamhane's T2 test was performed to adjust for multiple comparisons between groups within each analysis.ResultsThe subfoveal CT (SFCT) in the high hypermetropic group was significantly thicker than that in normal controls (309.22 ± 53.14 μm vs. 291.27 ± 38.27 μm; P = 0.019). At 0.5 mm, 1.5 mm, and 3.0 mm in diameter, the nasal choroidal sectors of the high hyperopia eyes were significantly thicker than that of the control (P < 0.05). There was significant difference in the choroidal vascular parameters. TCA and LA in the high hyperopia eyes was significantly larger than that of the normal control eyes (3078129.54 ± 448271.18 μm2 vs. 2765218.17 ± 317827.19 μm2, 1926819.54 ± 229817.56 μm2 vs. 1748817.18 ± 191827.98 μm2; P = 0.009, P = 0.011; Table 2). SA values were 1086287.55 ± 212712.11 um2 in the high hyperopia eyes and 999712.71 ± 209838.12 μm2 in the control eyes. The CVI and LA/SA ratio values were differed significantly in the two groups (P = 0.019, P = 0.030, respectively). AL was significantly correlated with SFCT (r = −0.325, P = 0.047), but not significantly correlated with other parameters. Spherical equivalent (SE) was significantly correlated with AL and SFCT (r = −0.711, r = 0.311; P = 0.001, P = 0.016), whereas no significant association between sphere and other parameters.ConclusionThe choroidal structure of the high hyperopia eyes was different from the normal control eyes. The thicker SFCT, higher LA, and TCA were characteristic of high hyperopia eyes. Choroidal blood flow may be decreased in amblyopic eyes. SFCT of high hyperopia children abnormally increased and correlated with shorter AL and higher SE. AL and SE affect choroidal structure and vascular density

Nuclear export regulation of COP1 by 14-3-3σ in response to DNA damage

Mammalian constitutive photomorphogenic 1 (COP1) is a p53 E3 ubiquitin ligase involved in regulating p53 protein level. In plants, the dynamic cytoplasm/nucleus distribution of COP1 is important for its function in terms of catalyzing the degradation of target proteins. In mammalian cells, the biological consequence of cytoplasmic distribution of COP1 is not well characterized. Here, we show that DNA damage leads to the redistribution of COP1 to the cytoplasm and that 14-3-3σ, a p53 target gene product, controls COP1 subcellular localization. Investigation of the underlying mechanism suggests that COP1 S387 phosphorylation is required for COP1 to bind 14-3-3σ. Significantly, upon DNA damage, 14-3-3σ binds to phosphorylated COP1 at S387, resulting in COP1's accumulation in the cytoplasm. Cytoplasmic COP1 localization leads to its enhanced ubiquitination. We also show that N-terminal 14-3-3σ interacts with COP1 and promotes COP1 nuclear export through its NES sequence. Further, we show that COP1 is important in causing p53 nuclear exclusion. Finally, we demonstrate that 14-3-3σ targets COP1 for nuclear export, thereby preventing COP1-mediated p53 nuclear export. Together, these results define a novel, detailed mechanism for the subcellular localization and regulation of COP1 after DNA damage and provide a mechanistic explanation for the notion that 14-3-3σ's impact on the inhibition of p53 E3 ligases is an important step for p53 stabilization after DNA damage

Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes

The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3\u27UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The expression of Nup98 is reduced in murine and human hepatocellular carcinomas (HCCs) and correlates with p21 expression in HCC patients. Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins

Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production. Inhibition of mitochondrial respiratory complex I activity by IACS-010759 selectively suppressed cellular respiration and cell proliferation of RTS osteoblasts. Furthermore, systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes. In summary, our study suggests that mitochondrial respiratory complex I is a potential therapeutic target for RTS-associated osteosarcoma and provides future insights for clinical treatment strategies

Antimicrobial peptide temporin derivatives inhibit biofilm formation and virulence factor expression of Streptococcus mutans

IntroductionTemporin-GHa obtained from the frog Hylarana guentheri showed bactericidal efficacy against Streptococcus mutans. To enhance its antibacterial activity, the derived peptides GHaR and GHa11R were designed, and their antibacterial performance, antibiofilm efficacy and potential in the inhibition of dental caries were evaluated.MethodsBacterial survival assay, fluorescent staining assay and transmission electron microscopy observation were applied to explore how the peptides inhibited and killed S. mutans. The antibiofilm efficacy was assayed by examining exopolysaccharide (EPS) and lactic acid production, bacterial adhesion and cell surface hydrophobicity. The gene expression level of virulence factors of S. mutans was detected by qRT-PCR. Finally, the impact of the peptides on the caries induced ability of S. mutans was measured using a rat caries model.ResultsIt has been shown that the peptides inhibited biofilm rapid accumulation by weakening the initial adhesion of S. mutans and reducing the production of EPS. Meanwhile, they also decreased bacterial acidogenicity and aciduricity, and ultimately prevented caries development in vivo.ConclusionGHaR and GHa11R might be promising candidates for controlling S. mutans infections

Regulation of Embryonic and Induced Pluripotency by Aurora Kinase-p53 Signaling

SummaryMany signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. Depletion of one such molecule, aurora kinase A (Aurka), resulted in compromised self-renewal and consequent differentiation. By integrating global gene expression and computational analyses, we discovered that loss of Aurka leads to upregulated p53 activity that triggers ESC differentiation. Specifically, Aurka regulates pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impairs p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming. Our studies demonstrate an essential role for Aurka-p53 signaling in the regulation of self-renewal, differentiation, and somatic cell reprogramming

O2 adsorbed on Ptn clusters: Structure and optical absorption

The interaction of O2 with Ptn and the optical absorption properties of PtnO2 were explored under the framework of density functional theory. The Ptn (n= 2, 4, 6, 9, 10, 14, 18, 22, and 27) clusters were selected, which were reported as magnetic number Ptn clusters in reference (V. Kumar and Y. Kawazoe, Phys. Rev. B 77(20), 205418 (2008)). The single Pt atom was also considered. The longest O2 bonds were found for Pt27O2, Pt6O2 and Pt14O2, while PtO2 and Pt2O2 have the shortest O2 bonds. This result showed that the single Pt atom was not preferred for O2 activation. The O2 bond length was closely related to the electron transfer from Ptn to O2. The optical absorptions of PtnO2 were investigated with time-dependent density functional theory method. A new term of charge transfer strength was defined to estimate the further electron transfer from Ptn to O2 caused by the optical absorption in the visible light range. Our calculations showed that with the increasing n, the further electron transfer from Ptn to O2 caused by optical absorption will become very weak

Optimal Design of Adaptive Robust Control for the Delta Robot with Uncertainty: Fuzzy Set-Based Approach

An optimal control design for the uncertain Delta robot is proposed in the paper. The uncertain factors of the Delta robot include the unknown dynamic parameters, the residual vibration disturbances and the nonlinear joints friction, which are (possibly fast) time-varying and bounded. A fuzzy set theoretic approach is creatively used to describe the system uncertainty. With the fuzzily depicted uncertainty, an adaptive robust control, based on the fuzzy dynamic model, is established. It designs an adaptation mechanism, consisting of the leakage term and the dead-zone, to estimate the uncertainty information. An optimal design is constructed for the Delta robot and solved by minimizing a fuzzy set-based performance index. Unlike the traditional fuzzy control methods (if-then rules-based), the proposed control scheme is deterministic and fuzzily optimized. It is proven that the global solution in the closed form for this optimal design always exists and is unique. This research provides the Delta parallel robot a novel optimal control to guarantee the system performance regardless of the uncertainty. The effectiveness of the proposed control is illustrated by a series of simulation experiments. The results reveal that the further applications in other robots are feasible