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Scutellaria, or skullcaps, are medicinally important herbs in China, India, Japan, and elsewhere. Though Scutellaria is the second largest and one of the more taxonomically challenging genera within Lamiaceae, few molecular systematic studies have been undertaken within the genus; in part due to a paucity of available informative markers. The lack of informative molecular markers for Scutellaria hinders our ability to accurately and robustly reconstruct phylogenetic relationships, which hampers our understanding of the diversity, phylogeny, and evolutionary history of this cosmopolitan genus. Comparative analyses of 15 plastomes, representing 14 species of subfamily Scutellarioideae, indicate that plastomes within Scutellarioideae contain about 151,000 nucleotides, and possess a typical quadripartite structure. In total, 590 simple sequence repeats, 489 longer repeats, and 16 hyper-variable regions were identified from the 15 plastomes. Phylogenetic relationships among the 14 species representing four of the five genera of Scutellarioideae were resolved with high support values, but the current infrageneric classification of Scutellaria was not supported in all analyses. Complete plastome sequences provide better resolution at an interspecific level than using few to several plastid markers in phylogenetic reconstruction. The data presented here will serve as a foundation to facilitate DNA barcoding, species identification, and systematic research within Scutellaria, which is an important medicinal plant resource worldwide.

SQUAMOSA promoter-binding protein-like (SPL), as plant specific transcription factors, is involved in many plant growth and development processes. However, there is less systematical study for SPL transcription factor in B. juncea (Cruciferae). Here, a total of 59 SPL genes classified into eight phylogenetic groups were identified in B. juncea, highly conserved within each ortholog were also found based on gene structure, conserved motif, as well as clustering level. In addition, clustering of SPL domain showed that two zinc finger-like structures and NLS segments were identified in almost of BjuSPLs. Analyzed of putative cis-elements for BjuSPLs demonstrated that SPL transcription factors were involved in adverse environmental changes, such as light, plant stresses and phytohormones response. Expression analysis showed that differentially expressed SPL genes were identified in flower and stem development of Cruciferae; such as BjuSPL3a-B, BjuSPL2b_B and BjuSPL2c_A were significantly expressed in flower; BjuSPL 3b_B and BjuSPL10a_A were significantly expressed in stem node (VP: vegetative period). Moreover, 28 of the 59 BjuSPLs were found involved in their posttranscriptional regulation targeted by miR156. We demonstrated that miR156 negatively regulated BjuSPL10a_A and BjuSPL3b_B to act for stem development in B. juncea.

With the rapid development of the internet, social media has become an essential tool for getting information, and attracted a large number of people join the social media platforms because of its low cost, accessibility and amazing content. It greatly enriches our life. However, its rapid development and widespread also have provided an excellent convenience for the range of fake news, people are constantly exposed to fake news and suffer from it all the time. Fake news usually uses hyperbole to catch people's eyes with dishonest intention. More importantly, it often misleads the reader and causes people to have wrong perceptions of society. It has the potential for negative impacts on society and individuals. Therefore, it is significative research on detecting fake news. In the paper, we built a model named SMHA-CNN (Self Multi-Head Attention-based Convolutional Neural Networks) that can judge the authenticity of news with high accuracy based only on content by using convolutional neural networks and self multi-head attention mechanism. In order to prove its validity, we conducted experiments on a public dataset and achieved a precision rate of 95.5% with a recall rate of 95.6% under the 5-fold cross-validation. Our experimental result indicates that the model is more effective at detecting fake news.

As an erosional landform, the formation processes of Danxia landform are controlled by internal and external forces as well as lithologic properties. Using field data, we studied the role of lithologic properties on the formation of Danxia landform in Kongtongshan National Geopark, northwest China, through a series of experiments, including uniaxial compressive strength, identification analysis under polarizing microscope, X-ray diffraction analysis, inductively coupled plasma-mass spectrometry analysis, and scanning electron microscopy. The results show that the diagenesis degree, mineral composition, cement composition, degree of cementation, geochemical composition and element contents, and micro-structure influenced the structure and anti-weathering and anti-erosion abilities of the Danxia rock mass. Differential weathering of rock in different environments was an important force shaping the different types of Danxia landform. Weathering failure of the Danxia rock mass was the result of multiple combined factors; as well as lithology, other factors, such as those induced during tectonic uplift (i.e., faulting, jointing, and fracturing) and climate, cannot be neglected. Therefore, lithology played an important role in the structural development of Danxia landform, and different lithologies influenced its weathering rate and formation processes. Our findings can provide a reference for revealing the microscopic development of Danxia landform in arid and semi-arid areas.

The prevalence of allergic rhinitis (AR) in China has increased with an apparent geographic variation. The current study aims to investigate the AR prevalence/classification, diagnosis/treatment conditions, trigger factors, and risk factors in the general population of Guangzhou, the third biggest city in China. A cross-sectional survey was performed in the citizens in Guangzhou from December 2009 to March 2010 by using a stratified multistage cluster sampling method. All subjects were asked to complete a comprehensive questionnaire via a face to face interview. A total of 9,899 questionnaires were valid. The prevalence rate of AR in the general population of Guangzhou was 6.24%, with a significant higher prevalence in urban area (8.32%) versus rural area (3.43%). Among the AR subjects, most (87%) were diagnosed with intermittent AR and 87% suffered from moderate-severe symptoms. High percentages of the AR patients did not have previously physician-based diagnosis (34%) or specific medical treatment (55%). Morning time, winter season, and cold air were the most common trigger factors of AR. Family history of AR, current living place, living place during babyhood, smoking, home renovation, and pet ownership were the significant risk factors associated with AR prevalence in the population. The study demonstrated comprehensive epidemiological and clinical information about the AR in Guangzhou population. Change of living environment and lifestyles had strong impacts on the prevalence of AR. Public health policies should help the patients benefit from a proper diagnosis/treatment and specifically target the local risk factors, in order to control the AR incidence.

Prognosis of patients with colorectal cancer (CRC) is generally poor because of the lack of simple, convenient, and noninvasive tools for CRC detection at the early stage. The discovery of microRNAs (miRNAs) and their different expression profiles among different kinds of diseases has opened a new avenue for tumor diagnosis. We built a serum microRNA expression profile signature and tested its specificity and sensitivity as a biomarker in the diagnosis of CRC. We also studied its possible role in monitoring the progression of CRC. We conducted a two phase case-control test to identify serum miRNAs as biomarkers for CRC diagnosis. Using quantitative reverse transcription polymerase chain reactions, we tested ten candidate miRNAs in a training set (30 CRCs vs 30 controls). Risk score analysis was used to evaluate the diagnostic value of the serum miRNA profiling system. Other independent samples, including 83 CRCs and 59 controls, were used to validate the diagnostic model. In the training set, six serum miRNAs (miR-21, let-7g, miR-31, miR-92a, miR-181b, and miR-203) had significantly different expression levels between the CRCs and healthy controls. Risk score analysis demonstrated that the six-miRNA-based biomarker signature had high sensitivity and specificity for distinguishing the CRC samples from cancer-free controls. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA signature profiles were 0.900 and 0.923 for the two sets of serum samples, respectively. However, for the same serum samples, the areas under the ROC curve used by the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were only 0.649 and 0.598, respectively. The expression levels of the six serum miRNAs were also correlated with CRC progression. Thus, the identified six-miRNA signature can be used as a noninvasive biomarker for the diagnosis of CRC, with relatively high sensitivity and specificity.

Intronic microRNAs (in-miRNAs) as a class of miRNA family that regulates gene expression are still poorly understood in plants. In this study, we systematically identified rice in-miRNAs by re-mining eight published small RNA-sequencing datasets of rice. Furthermore, based on the collected expression, annotation, and putative target data, we investigated the structures, potential functions, and expression features of these in-miRNAs and the expression patterns of their host genes. A total of 153 in-miRNAs, which account for over 1/4 of the total rice miRNAs, were identified. In silico expression analysis showed that most of them (∼63%) are tissue or stage-specific. However, a majority of their host genes, especially those containing clustered in-miRNAs, exhibit stable high-level expressions among 513 microarray datasets. Although in-miRNAs show diversity in function and mechanism, the DNA methylation directed by 24 nt in-miRNAs may be the main pathway that controls the expressions of target genes, host genes, and even themselves. These findings may enhance our understanding on special functions of in-miRNAs, especially in mediating DNA methylation that was concluded to affect the stability of expression and structure of host and target genes.

The first comprehensive molecular phylogenetic reconstruction of the Cichorieae subtribe Lactucinae is provided. Sequences for two datasets, one of the nuclear rDNA ITS region, the other of five concatenated non-coding chloroplast DNA markers including the petD region and the psbA-trnH, 5'trnL((UAA))-trnF, rpl32-trnL((UAG)) and trnQ((UUG))-5'rps16 spacers, were, with few exceptions, newly generated for 130 samples of 78 species. The sampling spans the entire subtribe Lactucinae while focusing on its Chinese centre of diversity; more than 3/4 of the Chinese Lactucinae species are represented. The nuclear and plastid phylogenies inferred from the two independent datasets show various hard topological incongruences. They concern the internal topology of major lineages, in one case the placement of taxa in major lineages, the relationships between major lineages and even the circumscription of the subtribe, indicating potential events of ancient as well as of more recent reticulation and chloroplast capture in the evolution of the subtribe. The core of the subtribe is clearly monophyletic, consisting of the six lineages, Cicerbita, Cicerbita II, Lactuca, Melanoseris, Notoseris and Paraprenanthes. The Faberia lineage and the monospecific Prenanthes purpurea lineage are part of a monophyletic subtribe Lactucinae only in the nuclear or plastid phylogeny, respectively. Morphological and karyological support for their placement is considered. In the light of the molecular phylogenetic reconstruction and of additional morphological data, the conflicting taxonomies of the Chinese Lactuca alliance are discussed and it is concluded that the major lineages revealed are best treated at generic rank. An improved species level taxonomy of the Chinese Lactucinae is outlined; new synonymies and some new combinations are provided.

The binding of renin or prorenin to the (pro)renin receptor (PRR) promotes angiotensin (Ang) II formation and mediates Ang II-independent signaling pathways. In the central nervous system (CNS), Ang II regulates blood pressure via inducing oxidative stress; however, the role of PRR-mediated Ang II-independent signaling pathways in oxidative stress in the CNS remains undefined. To address this question, Neuro-2A cells were infected with control virus or an adeno-associated virus encoding the human PRR. Human PRR over-expression alone increased ROS levels, NADPH oxidase activity, as well as NADPH oxidase (NOX) isoforms 2 and 4 mRNA expression levels and these effects were not blocked by losartan. Moreover, the increase in NOX 2 and NOX 4 mRNA levels, NADPH oxidase activity, and ROS levels induced by PRR over-expression was prevented by mitogen activated protein kinase/extracellular signal-regulated kinase 1 and 2 (MAPK/ERK1/2) inhibition, and phosphoinositide 3 kinase/Akt (IP3/Akt) inhibition, indicating that PRR regulates NOX activity and ROS formation in neuro-2A cells through Ang II-independent ERK1/2 and IP3/Akt activation. Interestingly, at a concentration of 2 nM or higher, prorenin promoted Ang II formation, and thus further increased the ROS levels in cultured Neuro-2A cells via PRR. In conclusion, human PRR over-expression induced ROS production through both angiotensin II-dependent and -independent mechanisms. We showed that PRR-mediated angiotensin II-independent ROS formation is associated with activation of the MAPK/ERK1/2 and PI3/Akt signaling pathways and up-regulation of mRNA level of NOX 2 and NOX4 isoforms in neuronal cells.

Reducing harm associated with selling and purchasing sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote sexual health among female sex workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female sex workers to collectively organize, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female sex workers in South China to determine their potential for sexual health promotion.Semi-structured interviews with 34 low-income female sex workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and health-seeking behaviors, and dealing with violent clients. These data suggested that sex worker's laoxiang (hometown social connections) were more powerful than relationships between women selling sex at the same venue in establishing the terms and risk of commercial sex. Female sex workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations, including collective mobilization, condom promotion, violence mitigation, and promotion of health-seeking behaviors. Outreach members observed that sex workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local sexual health services.Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for sex worker health programs. Further research on dyadic interpersonal relationships between female sex workers, group dynamics and norm establishment, and the social network characteristics are needed.

Background: Reducing harm associated with selling and purchasing sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote sexual health among female sex workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female sex workers to collectively organize, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female sex workers in South China to determine their potential for sexual health promotion. Methods/Principal Findings: Semi-structured interviews with 34 low-income female sex workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and healthseeking behaviors, and dealing with violent clients. These data suggested that sex worker's laoxiang (hometown social connections) were more powerful than relationships between women selling sex at the same venue in establishing the terms and risk of commercial sex. Female sex workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations, including collective mobilization, condom promotion, violence mitigation, and promotion of health-seeking behaviors. Outreach members observed that sex workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local sexual health services. Conclusions/Significance: Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for sex worker health programs. Further research on dyadic interpersonal relationships between female sex workers, group dynamics and norm establishment, and the social network characteristics are needed. [ABSTRACT FROM AUTHOR]

Multistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.

Human beings are exposed to compressed air or a nitrogen-oxygen mixture, they will produce signs and symptoms of nitrogen narcosis such as amnesia or even loss of memory, which may be disappeared once back to the normobaric environment. This study was designed to investigate the effect of nitrogen narcosis induced by repetitive hyperbaric nitrogen-oxygen mixture exposure on long-term cognitive function in newborn mice and the underlying mechanisms. The electroencephalogram frequency was decreased while the amplitude was increased in a pressure-dependent manner during 0.6, 1.2, 1.8 MPa (million pascal) nitrogen-oxygen mixture exposures in adult mice. Nitrogen narcosis in postnatal days 7-9 mice but not in adult mice induced by repetitive hyperbaric exposure prolonged the latency to find the platform and decreased the number of platform-site crossovers during Morris water maze tests, and reduced the time in the center during the open field tests. An increase in the expression of cleaved caspase-3 in the hippocampus and cortex were observed immediately on the first day after hyperbaric exposure, and this lasted for seven days. Additionally, nitrogen narcosis induced loss of the dendritic spines but not of the neurons, which may mainly account for the cognitive dysfunction. Nitrogen narcosis induced long-term cognitive and emotional dysfunction in the postnatal mice but not in the adult mice, which may result from neuronal apoptosis and especially reduction of dendritic spines of neurons.

OBJECTIVE:To evaluate the prognostic effects of combining serum circulating tumor cells (CTCs) and squamous cell carcinoma antigen (SCC-Ag) levels on patients with locally advanced cervical cancer treated with radiotherapy. METHODS:Ninety-nine patients with locally advanced cervical cancer ([FIGO] stage IIB-IVA) undergoing radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) were identified. The association between serum CTC level and clinicopathological parameters was examined. Univariate and multivariate survival analyses were performed by using Cox's proportional hazards regression model. RESULTS:Elevated CTC and SCC-Ag levels were significantly associated with poor disease-free survival (DFS). Multivariate analysis suggest that serum CTC level, FIGO stage and serum SCC-Ag level were independent prognostic factors for two-year DFS. When CTC and SCC-Ag levels were combined into a new risk model to predict disease progression of cervical cancer patients, it performed a significantly better predictive efficiency compared with either biomarker alone. CONCLUSION:Serum CTC and SCC-Ag levels are potentially useful biomarkers for prediction of prognosis in locally advanced cervical cancer patients and their combination significantly improves predictive ability for survival in locally advanced cervical cancer patients.

BACKGROUND:Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. METHODS:Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical-pathological parameters was examined. Univariate and multivariate survival analyses were performed. FINDINGS:The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. CONCLUSION:The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant metastasis-free survival in patients with NPC.

This study aimed to clarify changes in the prevalence of rheumatic diseases in Shantou, China, in the past 3 decades and validate whether stair-climbing is a risk factor for knee pain and knee osteoarthritis (KOA). The World Health Organization-International League Against Rheumatism Community Oriented Program for Control of Rheumatic Diseases (COPCORD) protocol was implemented. In all, 2337 adults living in buildings without elevators and 1719 adults living in buildings with elevators were surveyed. The prevalence of rheumatic pain at any site and in the knee was 15.7% and 10.2%, respectively; both types of pain had a significantly higher incidence in residents of buildings without elevators than was reported by people who lived in buildings with elevators (14.9% vs. 10.6% and 11.32% vs. 8.82%, respectively) (both P < 0.0001). The prevalence of rheumatic pain in the neck, lumbar spine, shoulder, elbow, and foot was 5.6%, 4.5%, 3.1%, 1.4%, and 1.8%, respectively; these findings were similar to the data from the 1987 rural survey, but were somewhat lower than data reported in the urban and suburban surveys of the 1990s, with the exception of neck and lumbar pain. The prevalence of KOA, gout, and fibromyalgia was 7.10%, 1.08%, and 0.07%, respectively, and their prevalence increased significantly compared with those in previous studies from the 20th century. There were no significant differences in the prevalence of rheumatoid arthritis (RA) (0.35%) or ankylosing spondylitis (AS) (0.31%) compared to that reported in prior surveys. The prevalence of KOA was higher in for residents of buildings without elevators than that in those who had access to elevators (16-64 years, 5.89% vs. 3.95%, P = 0.004; 16->85 years, 7.64% vs. 6.26%, P = 0.162). The prevalence of RA and AS remained stable, whereas that of KOA, gout, and fibromyalgia has increased significantly in Shantou, China, during the past 3 decades. Stair-climbing might be an important risk factor for knee pain and KOA.

Copy number variation (CNV) has been reported to be associated with disease and various cancers. Hence, identifying the accurate position and the type of CNV is currently a critical issue. There are many tools targeting on detecting CNV regions, constructing haplotype phases on CNV regions, or estimating the numerical copy numbers. However, none of them can do all of the three tasks at the same time. This paper presents a method based on Hidden Markov Model to detect parent specific copy number change on both chromosomes with signals from SNP arrays. A haplotype tree is constructed with dynamic branch merging to model the transition of the copy number status of the two alleles assessed at each SNP locus. The emission models are constructed for the genotypes formed with the two haplotypes. The proposed method can provide the segmentation points of the CNV regions as well as the haplotype phasing for the allelic status on each chromosome. The estimated copy numbers are provided as fractional numbers, which can accommodate the somatic mutation in cancer specimens that usually consist of heterogeneous cell populations. The algorithm is evaluated on simulated data and the previously published regions of CNV of the 270 HapMap individuals. The results were compared with five popular methods: PennCNV, genoCN, COKGEN, QuantiSNP and cnvHap. The application on oral cancer samples demonstrates how the proposed method can facilitate clinical association studies. The proposed algorithm exhibits comparable sensitivity of the CNV regions to the best algorithm in our genome-wide study and demonstrates the highest detection rate in SNP dense regions. In addition, we provide better haplotype phasing accuracy than similar approaches. The clinical association carried out with our fractional estimate of copy numbers in the cancer samples provides better detection power than that with integer copy number states.

MicroRNAs (miRNAs) have a major impact on regulatory networks in human carcinogenesis. In this study, we sought to investigate the prognostic significance of miRNAs in patients with oral cavity squamous cell carcinoma (OSCC). In a discovery phase, RNA was extracted from 58 OSCC tumor samples and paired normal tissues. MiRNAs expression was evaluated with TaqMan Array Card and TaqMan MicroRNA assays. The prognostic significance of the miRNA signature identified in the discovery phase was validated by qRT-PCR in a replication set consisting of 141 formalin-fixed, paraffin-embedded (FFPE) samples. We identified a miRNA regulatory network centered on the three hub genes (SP1, MYC, and TP53) that predicted distinct clinical endpoints. Three miRNAs (miR-218, miR-125b, and let-7g) and their downstream response genes had a concordant prognostic significance on disease-free survival and disease-specific survival rates. In addition, patients with a reduced expression of miR-218, miR-125b, and let-7g have a higher risk of poor outcomes in presence of specific risk factors (p-stage III-IV, pT3-4, or pN+). Our findings indicate that specific miRNAs have prognostic significance in OSCC patients and may improve prognostic stratification over traditional risk factors.

Rod and cone photoreceptor neurons in the mammalian retina possess specialized cellular architecture and functional features for converting light to a neuronal signal. Establishing and maintaining these characteristics requires appropriate expression of a specific set of genes, which is tightly regulated by a network of photoreceptor transcription factors centered on the cone-rod homeobox protein CRX. CRX recruits transcription coactivators p300 and CBP to acetylate promoter-bound histones and activate transcription of target genes. To further elucidate the role of these two coactivators, we conditionally knocked out Ep300 and/or CrebBP in differentiating rods or cones, using opsin-driven Cre recombinase. Knockout of either factor alone exerted minimal effects, but loss of both factors severely disrupted target cell morphology and function: the unique nuclear chromatin organization seen in mouse rods was reversed, accompanied by redistribution of nuclear territories associated with repressive and active histone marks. Transcription of many genes including CRX targets was severely impaired, correlating with reduced histone H3/H4 acetylation (the products of p300/CBP) on target gene promoters. Interestingly, the presence of a single wild-type allele of either coactivator prevented many of these defects, with Ep300 more effective than Cbp. These results suggest that p300 and CBP play essential roles in maintaining photoreceptor-specific structure, function and gene expression.

Molecular methods for predicting prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are urgently needed, considering its high recurrence rate and tendency for metastasis. The present study investigated the genetic basis of variations in gene expression associated with poor prognosis in OSCC using Affymetrix SNP 6.0 and Affymetrix GeneChip Human Gene 1.0 ST arrays. We identified recurrent DNA amplifications scattered from 8q22.2 to 8q24.3 in 112 OSCC specimens. These amplicons demonstrated significant associations with increased incidence of extracapsular spread, development of second primary malignancies, and poor survival. Fluorescence in situ hybridization, in a validation panel consisting of 295 cases, confirmed these associations. Assessment of the effects of copy number variations (CNVs) on genome-wide variations in gene expression identified a total of 85 CNV-associated transcripts enriched in the MYC-centered regulatory network. Twenty-four transcripts associated with increased risk of second primary malignancies, tumor relapse, and poor survival. Besides MYC itself, a novel dysregulated MYC module plays a key role in OSCC carcinogenesis. This study identified a candidate molecular signature associated with poor prognosis in OSCC patients, which may ultimately facilitate patient-tailored selection of therapeutic strategies.