Identifying critical differentiation state of MCF-7 cells for breast cancer by dynamical network biomarkers

Identifying the pre-transition state just before a critical transition during a complex biological process is a challenging task, because the state of the system may show neither apparent change nor clear phenomenon before this critical transition during the biological process. By exploring rich correlation information provided by high-throughput data, the dynamical network biomarker (DNB) can identify the pre-transition state. In this work, we apply DNB to detect an early-warning signals of breast cancer on the basis of gene expression data of MCF-7 cell differentiation. We find a number of the related modules and pathways in the samples, which can be used not only as the biomarkers of cancer cells but also as the drug targets. Both functional and pathway enrichment analyses validate the results

Proteomic analyses provide novel insights into plant growth and ginsenoside biosynthesis in forest cultivated Panax ginseng (F. Ginseng)

F. Ginseng (Panax ginseng) is planted in the forest to enhance the natural ginseng resources, which have an immense medicinal and economic value. The morphology of the cultivated plants becomes similar to that of wild growing ginseng (W. Ginseng) over the years. So far, there have been no studies highlighting the physiological or functional changes in F. Ginseng and its wild counterparts. In the present study, we used proteomic technologies (2DE and iTRAQ) coupled to mass spectrometry to compare W. Ginseng and F. Ginseng at various growth stages. Hierarchical cluster analysis based on protein abundance revealed that the protein expression profile of 25-year-old F. Ginseng was more like W. Ginseng than less 20-year-old F. Ginseng. We identified 192 differentially expressed protein spots in F. Ginseng. These protein spots increased with increase in growth years of F. Ginseng and were associated with proteins involved in energy metabolism, ginsenosides biosynthesis, and stress response. The mRNA, physiological, and metabolic analysis showed that the external morphology, protein expression profile, and ginsenoside synthesis ability of the F. Ginseng increased just like that of W. Ginseng with the increase in age. Our study represents the first characterization of the proteome of F. Ginseng during development and provides new insights into the metabolism and accumulation of ginsenosides

Age and Racial Differences Among PSA-Detected (AJCC Stage T1cN0M0) Prostate Cancer in the U.S.: A Population-Based Study of 70,345 Men

Purpose: Few studies have evaluated the risk profile of PSA-detected T1cN0M0 prostate cancer, defined as tumors diagnosed by needle biopsy because of elevated PSA levels without other clinical signs of disease. However, some men with stage T1cN0M0 prostate cancer may have high-risk disease, thus experiencing inferior outcomes as predicted by a risk group stratification model.Methods: We identified men diagnosed with stage T1cN0M0 prostate cancer from 2004-2008 reported to the SEER program. Multivariate logistic regression was used to model the probability of intermediate-risk (PSA >10 ng/ml but < 20 ng/ml and/or GS 7), and high-risk disease (PSA >20 ng/ml, and/or GS ≥8), relative to low-risk disease (PSA <10 ng/ml and GS ≤6), adjusting for age, race, marital status, median household income, and area of residence. Results: A total of 70,345 men with PSA-detected T1cN0M0 prostate cancer were identified. Of these, 47.6%, 35.9%, and 16.5% presented with low-, intermediate-, and high-risk disease, respectively. At baseline (50 years of age), risk was higher for black men than for whites for high-risk disease (OR 3.31, 95% CI 2.85-3.84). The ORs for age (per year) for high-risk disease relative to low-risk disease were 1.09 (95% CI 1.09-1.10) for white men, and as 1.06 (95% CI 1.05-1.07) for black men. Further, among a subgroup of men with low PSA (<10 ng/ml) T1cN0M0 prostate cancer, risk was also higher for black man than for white men at baseline (50 years of age) (OR 2.70, 95% CI 2.09-3.48). The ORs for age (per year) for high-risk disease relative to low-risk disease were 1.09 (95% CI 1.09-1.10) for white men, and as 1.06 (95% CI 1.05-1.07) for black men.Conclusions: A substantial proportion of men with PSA-detected prostate cancer as reported to the SEER program had high-risk disease. Black race and older age were associated with a greater likelihood of high-risk disease

Comparative proteomic analysis of soybean leaves and roots by iTRAQ provides insights into response mechanisms to short-term salt stress

Salinity severely threatens land use capability and crop yields worldwide. Understanding the mechanisms that protect soybean from salt stress will help in the development of salt-stress tolerant leguminous plants. Here we firstly analyzed the changes in malondialdehyde levels, the activities of superoxide dismutase and peroxidases, cholorophyll contents, and Na+/K+ ratios in leaves and roots from soybean seedlings treated with 200 mM NaCl for different time points, and suggested that 200 mM NaCl treated for 12 h was enough for exploring proteomic analysis to soybean seedlings. iTRAQ-based proteomic approach was used to investigate the proteomes of soybean leaves and roots under salt treatment. Data are available via ProteomeXchange with identifier PXD002851. In total, 278 and 440 proteins with significantly altered abundance were identified in leaves and roots of soybean, respectively, with only 50 mutual unique proteins in the both tissues. These identified differentially expressed proteins (DEPs) were mainly involved in 13 biological processes. Moreover, protein-protein interaction analysis revealed that the proteins involved in metabolism, carbohydrate and energy metabolism, protein synthesis and redox homeostasis constructed four types of response networks to high salt stress. Besides, semi-quantitative RT-PCR analysis revealed that some of the proteins, such as 14-3-3, MMK2, PP1, TRX-h, were also regulated by salt stress at the level of transcription. These results indicated that effective regulatory protein expression related to signalling, membrane and transport, stress defense and metabolism played important roles in the short-term salt response of soybean seedlings

Chemical Exchange Saturation Transfer MR Imaging Is Superior to Diffusion Tensor Imaging in the Diagnosis and Severity Evaluation of Parkinson's Disease: a Study on Substantia Nigra and Striatum

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by nigrostriatal cell loss. To date the diagnosis of PD is still based primarily on the clinical manifestations which may be typical and obvious only in advanced-stage PD. Thus, it is crucial to find a reliable marker for the diagnosis of PD. We conducted this study to assess the diagnostic efficiency of chemical-exchange-saturation-transfer (CEST) imaging and diffusion-tensor imaging (DTI) in PD at 3 Tesla by evaluating changes on substantia nigra and striatum. Twenty-three PD patients and twenty-three age-matched normal controls were recruited. All patients and controls were imaged on a 3 Tesla MR system, using an 8-channel head coil. CEST imaging was acquired in two transverse slices of the head, including substantia nigra and striatum. The magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym(3.5ppm), and the total CEST signal intensity between 0 and 4 ppm were calculated. Multi-slice DTI was acquired for all the patients and normal controls. Quantitative analysis was performed on the substantia nigra, globus pallidus, putamen and caudate. The MTRasym(3.5ppm) value, the total CEST signal intensity and fractional anisotropy (FA) value of the substantia nigra were all significantly lower in PD patients than in normal controls (P = 0.003, P = 0.004 and P < 0.001, respectively). The MTRasym(3.5ppm) values of the putamen and the caudate were significantly higher in PD patients than in normal controls (P = 0.010 and P = 0.009, respectively). There were no significant differences for the mean diffusivity (MD) in these four regions between PD patients and normal controls. In conclusion, CEST MR imaging provided multiple CEST image contrasts in the substantia nigra and the striatum in PD and may be superior to DTI in the diagnosis of PD

Isolation and functional characterization of bidirectional promoters in rice

Bidirectional promoters, which show great application potential in genetic improvement of plants, have aroused great research interest recently. However, most bidirectional promoters were cloned individually in the studies of single genes. Here, we initiatively combined RNA-seq data and cDNA microarray data to discover the potential bidirectional promoters in rice genome. Based on the expression level and correlation of each adjacent and oppositely transcribed gene pair, we selected four candidate gene pairs. Then, the intergenic region between each pair was isolated and cloned into a dual reporter vector pDX2181 for functional identification. GUS and GFP assays of the transgenic plants indicated that all the intergenic regions showed bidirectional expression activity in various tissues. Through 5’ and 3’ deletion analysis on one of the above bidirectional promoters, we identified the enhancing region which sharply increased its bidirectional expression efficiency and the essential regions respectively responsible for its 5’ and 3’ basic expression activity. The bidirectional arrangement of the four gene pairs in six gramineous plants was also analyzed, showing the conserved characteristics of the four bidirectional promoters identified in our study. In addition, two novel cis-sequences conserved in the four bidirectional promoters were discovered by bioinformatic identification. Our study proposes a feasible method for selecting, cloning and functionally identifying bidirectional promoters as well as for discovering their bidirectional regulatory regions and conserved sequences in rice

Hippocampal Transcriptome-Guided Genetic Analysis of Correlated Episodic Memory Phenotypes in Alzheimer&#39;s Disease

As the most common type of dementia, Alzheimer’s disease (AD) is a neurodegenerative disorder initially manifested by impaired memory performances. While the diagnosis information indicates a dichotomous status of a patient, memory scores have the potential to capture the continuous nature of the disease progression and may provide more insights into the underlying mechanism. In this work, we performed a targeted genetic study of memory scores on an AD cohort to identify the associations between a set of genes highly expressed in the hippocampal region and seven cognitive scores related to episodic memory. Both main effects and interaction effects of the targeted genetic markers on these correlated memory scores were examined. In addition to well-known AD genetic markers APOE and TOMM40, our analysis identified a new risk gene NAV2 through the gene-level main effect analysis. NAV2 was found to be significantly and consistently associated with all seven episodic memory scores. Genetic interaction analysis also yielded a few promising hits warranting further investigation, especially for the RAVLT list B Score

Origin, diversity and maturation of human antiviral antibodies analyzed by high-throughput sequencing

Our understanding of how antibodies are generated and function could help develop effective vaccines and antibody-based therapeutics against viruses such as HIV-1, SARS Coronavirus (CoV), and Hendra and Nipah viruses (henipaviruses). Although broadly neutralizing antibodies (bnAbs) against the HIV-1 were observed in patients, elicitation of such bnAbs remains a major challenge when compared to other viral targets. We previously hypothesized that HIV-1 could have evolved a strategy to evade the immune system due to absent or very weak binding of germline antibodies to the conserved epitopes that may not be sufficient to initiate and/or maintain an effective immune response. To further explore our hypothesis, we used the 454 sequence analysis of a large na&#239;ve library of human IgM antibodies which had been used for selecting antibodies against SARS Coronavirus (CoV) receptor-binding domain (RBD), and soluble G proteins (sG) of Hendra and Nipah viruses (henipaviruses). We found that the human IgM repertoires from the 454 sequencing have diverse germline usages, recombination patterns, junction diversity and a lower extent of somatic mutation. In this study, we identified germline intermediates of antibodies specific to HIV-1 and other viruses as observed in normal individuals, and compared their genetic diversity and somatic mutation level along with available structural and functional data. Further computational analysis will provide framework for understanding the underlying genetic and molecular determinants related to maturation pathways of antiviral bnAbs that could be useful for applying novel approaches to the design of effective vaccine immunogens and antibody-based therapeutics

Overexpression of an Apocynum venetum DEAD-box helicase gene (AvDH1) in cotton confers salinity tolerance and increases yield in a saline field

Soil salinity is a major environmental stress limiting plant growth and productivity. We have reported previously the isolation of an Apocynum venetum DEAD-box helicase 1 (AvDH1) that is expressed in response to salt exposure. Here, we report that the overexpression of AvDH1 driven by a constitutive cauliflower mosaic virus-35S promoter in cotton plants confers salinity tolerance. Southern and northern blotting analyses showed that the AvDH1 gene was integrated into the cotton genome and expressed. In this study, the growth of transgenic cotton expressing AvDH1 was evaluated under saline conditions in a growth chamber and in a saline field trial. Transgenic cotton overexpressing AvDH1 was much more resistant to salt than the wild-type plants when grown in a growth chamber. The lower membrane ion leakage, along with increased activity of superoxide dismutase (SOD), in AvDH1 transgenic lines suggested that these characteristics may prevent membrane damage, which increases plant survival rates. In a saline field, the transgenic cotton lines expressing AvDH1 showed increased boll numbers, boll weights and seed cotton yields compared with wild-type plants, especially at high soil salinity levels. This study indicates that transgenic cotton expressing AvDH1 is a promising option for increasing crop productivity in saline fields

Similarities and Differences in Decision-Making Impairments between Autism Spectrum Disorder and Schizophrenia

Although individuals with autism spectrum disorders (ASD) and schizophrenia (SCH) share overlapping characteristics and may perform similarly on many cognitive tasks, cognitive dysfunctions common to both disorders do not necessarily share the same underlying mechanisms. Decision making is currently a major research interest for both ASD and SCH. The aim of the present study was to make direct comparisons of decision making and disorder-specific underlying neuropsychological mechanisms between the two disorders. Thirty-seven participants with ASD, 46 patients with SCH and 80 healthy controls (HC) were assessed with the Iowa Gambling Task (IGT), which measures decision-making under ambiguity, and the Game of Dice Task (GDT), which measures decision-making under risk. The results revealed that both the ASD and SCH groups had deficits for both the IGT and GDT compared with the HC. More importantly, in the IGT, participants with ASD displayed a preference for deck A, indicating that they had more sensitivity to the magnitude of loss than to the frequency of loss, whereas patients with SCH displayed a preference for deck B, indicating that they showed more sensitivity to the frequency of loss than to the magnitude of loss. In the GDT, the impaired performance might be due to the deficits in executive functions in patients with SCH, whereas the impaired performance might be due to the deficits in feedback processing in participants with ASD. These findings demonstrate that there are similar impairments in decision-making tasks between ASD and SCH; however, these two disorders may have different impairment mechanisms