Overexpression of CHI3L1 is associated with chemoresistance and poor outcome of epithelial ovarian carcinoma.

We propose CHI3L1 as a prognostic biomarker for patients with epithelial ovarian carcinoma (EOC) and also suggest possible biological functions of CHI3L1. We measured CHI3L1 expression with quantitative real time-polymerase chain reaction (qRT-PCR) in 180 women with EOC and evaluated correlations between CHI3L1 expression, clinicopathological characteristics, and the outcomes of the patients. The expression of CHI3L1 was higher in cancerous tissues than in normal tissues. The expression of CHI3L1 was also higher in patients with a serous histological type, advanced stage, and chemoresistance. Patients with high CHI3L1 expression had a shorter progression-free survival (p < 0.001)and overall survival (p < 0.001). Patients with high CHI3L1 expression also had a high risk of recurrence (p < 0.001)and death (p < 0.001). In vitro studies showed that CHI3L1 up-regulated the expression of anti-apoptotic Mcl-1 protein and hampered paclitaxel-induced apoptosis of ovarian cancer cells. These results suggest that CHI3L1 shows potential as a prognostic biomarker for EOC. CHI3L1 may promote chemoresistance via inhibition of drug-induced apoptosis by up-regulating Mcl-1.

Insulin-like growth factors inhibit dendritic cell-mediated anti-tumor immunity through regulating ERK1/2 phosphorylation and p38 dephosphorylation.

Insulin-like growth factors (IGFs) can promote tumorigenesis via inhibiting the apoptosis of cancer cells. The relationship between IGFs and dendritic cell (DC)-mediated immunity were investigated. Advanced-stage ovarian carcinoma patients were first evaluated to show higher IGF-1 and IGF-2 concentrations in their ascites than early-stage patients. IGFs could suppress DCs' maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8(+) T cell. IGF-treated DCs also secreted higher concentrations of IL-10 and TNF-α. IGF-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The percentages of matured DCs in the ascites were significantly lower in the IGF-1 or IGF-2 highly-expressing WF-3 tumor-bearing mice. The IGF1R inhibitor - NVP-AEW541, could block the effects of IGFs to rescue DCs' maturation and to restore DC-mediated antigen-specific immunity through enhancing ERK1/2 phosphorylation and p38 dephosphorylation. IGFs can inhibit DC-mediated anti-tumor immunity through suppressing maturation and function and the IGF1R inhibitor could restore the DC-mediated anti-tumor immunity. Blockade of IGFs could be a potential strategy for cancer immunotherapy.

Detect AD Patients by Using EEG Coherence Analysis.

The purpose of this study is to discriminate mild Alzheimer's disease (AD) patients from the normal aging. The EEG coherence was applied to analyze the data from auditory oddball paradigm to discriminate the differences of corticocortical connections between mild AD patients and healthy subjects. The results showed that the lower values of coherence were performed in mild AD patients than in the normal aging subjects, especially in theta band. The implications and suggestions are shown in this study.

The reduction in σ-promoter recognition flexibility as induced by core RNAP is required for σ to discern the optimal promoter spacing.

Sigma (σ) factors are bacterial transcription initiation factors that direct transcription at cognate promoters. The promoters recognized by primary σ are composed of -10 and -35 consensus elements separated by a spacer of 17±1 bp for optimal activity. However, how the optimal promoter spacing is sensed by the primary σ remains unclear. In the present study, we examined this issue using a transcriptionally active Bacillus subtilis N-terminally truncated σA (SND100-σA). The results of the present study demonstrate that SND100-σA binds specifically to both the -10 and -35 elements of the trnS spacing variants, of which the spacer lengths range from 14 to 21 bp, indicating that simultaneous and specific recognition of promoter -10 and -35 elements is insufficient for primary σ to discern the optimal promoter spacing. Moreover, shortening in length of the flexible linker between the two promoter DNA-binding domains of σA also does not enable SND100-σA to sense the optimal promoter spacing. Efficient recognition of optimal promoter spacing by SND100-σA requires core RNAP (RNA polymerase) which reduces the flexibility of simultaneous and specific binding of SND100-σA to both promoter -10 and -35 elements. Thus the discrimination of optimal promoter spacing by σ is core-dependent.

Applying the Bispectral Analysis on Widespread Diffuse Cross-Frequency Interactive Effects.

The aim of this paper is applying the bispectral analysis on widespread diffuse cross-frequency interactive effects. The event-related potentials (ERPs) research method was used in this study and it could collect the widespread diffuse cross-frequency from mild cognitive impairment (MCI) patients' brain wave. In this study, the brain wave data were collected from 12 MCI subjects, 12 healthy elderly, and 12 healthy young. The findings showed that the decreased interhemispheric coherence of 8.8 Hz for MCI compared with healthy elderly in the central-parietal cortex to respective surrounding sites and each MCI subject showed significantly widespread diffuse pattern of cross-frequency interactions in comparison with the healthy controls in the left central-parietal and right frontal. This study provides some explanation and suggestions for these findings.

Age- and disease-related features of task-related brain oscillations by using mutual information.

The aim of this study was to investigate changes in task-related brain oscillations and corticocortical connections in patients with mild cognitive impairment (MCI) and those with normal aging using cross-mutual information (CMI) analysis. We hypothesized that task-related brain oscillations and corticocortical connections were affected by age- and disease-related changes, which could be reflected in the CMI analysis. Electroencephalogram (EEG) recordings were measured in 16 MCI patients, 15 healthy age-matched controls, and 16 healthy younger individuals. The frequencies and interhemispheric CMI data were estimated in all groups. The specific EEG rhythms measured were delta (δ), theta (θ), alpha (α), beta (ß), and gamma (γ) bands. Significant differences in δ, θ, α, and ß bands were observed between the younger and elderly groups. However, only the θ band was significantly different between the elderly and MCI groups. Moreover, this study used EEG recordings to investigate age- and disease-related changes in the corticocortical connections of the brain. This study proves that the θ-band frequency of the connection between the parietal and occipital lobes for the age- and disease-related changes can be depicted using the CMI analysis.

Age-related changes of task-specific brain activity in normal aging.

An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N=15; mean age 23.7±2.8 years) and older participants (N=15; mean age 70.1±7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices.

The core-independent promoter-specific interaction of primary sigma factor.

Previous studies have led to a model in which the promoter-specific recognition of prokaryotic transcription initiation factor, sigma (σ), is core dependent. Most σ functions were studied on the basis of this tenet. Here, we provide in vitro evidence demonstrating that the intact Bacillus subtilis primary sigma, σ(A), by itself, is able to interact specifically with promoter deoxyribonucleic acid (DNA), albeit with low sequence selectivity. The core-independent promoter-specific interaction of the σ(A) is -10 specific. However, the promoter -10 specific interaction is unable to allow the σ(A) to discern the optimal promoter spacing. To fulfill this goal, the σ(A) requires assistance from core RNA polymerase (RNAP). The ability of σ, by itself, to interact specifically with promoter might introduce a critical new dimension of study in prokaryotic σ function.

Role of the sigma factor in transcription initiation in the absence of core RNA polymerase.

Sigma factors (sigmas) are bacterial transcription factors that bind core RNA polymerase (RNAP) and direct transcription initiation at cognate promoter sites. However, most of their functions have been investigated in the context of RNAP. This has made the exact function of sigma, and the importance of core RNAP in modulating sigma function, ambiguous. Here we identify a Bacillus subtilis mutant sigma(A) that is independently capable of specific binding and melting of the promoter DNA. Interestingly, specific and independent promoter binding of sigma is sufficient for the temperature- and Mg(2+)-independent melting of promoter DNA around the transcription start site, in contrast to the temperature- and Mg(2+)-dependent melting by RNAP around the promoter -10 element. Thus core RNAP is able to negatively modulate the sigma-initiated melting of the transcription start site and, by sensing the changes in temperature and Mg(2+) concentration, to regulate the efficiency of promoter -10 melting.