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Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration and lncRNAs play important roles in regulating SC activities. Here, in this study, we identify PAM (Pax7 Associated Muscle lncRNA) that is induced in activated/proliferating SCs upon injury to promote SC proliferation as myoblast cells. PAM is generated from a myoblast-specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM SE to its inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes upregulation. Altogether, our findings identify PAM as a previously unknown lncRNA that regulates both SC proliferation and aging through its trans gene regulatory activity.

Self-incompatibility (SI), which has recurred during the evolution of plants, is one of the most important cross-pollination mating systems. Three S-loci have been reported in Brassicaceae, namely, Arabidopsis lyrata (Al), Brassica (Br), and Leavenworthia alabamica (La) S-loci. Here, through multi-genomic comparative analysis of 20 species, we revealed that the most ancient S-locus was formed prior to the divergence of Brassicaceae lineage I and II. It was retained and inherited by Arabidopsis, as the Al S-locus in Brassicaceae lineage I. Furthermore, we found that the Br S-locus, which has been widely used in the breeding of Brassica crops to generate hybrid seeds, was formed through segmental translocation (ST) in the hexaploid ancestor of Brassica in Brassicaceae lineage II. The Br S-locus was evolved through a ST from one of the triplicated ancestral S-locus paralogs in the Brassica hexaploidy ancestor, while the other two S-locus paralogs were lost. Together with the previous discovery that the La S-locus was formed through a secondary origin in Brassicaceae lineage I, we conclude the monophyletic origin of Al and Br S-loci and clarify the evolutionary route of S-loci in the Brassicaceae family. Our findings will contribute to evolutionary studies and breeding applications of the S-locus in Brassicaceae.

Rubus corchorifolius (‘Shanmei’ or mountain berry, 2n =14) is widely distributed in China, and its fruit has high nutritional and medicinal values. Here, we report a high-quality chromosome-scale genome assembly of Shanmei, with a size of 215.69 Mb and encompassing 26,696 genes. Genome comparisons among Rosaceae species show that Shanmei and Fupenzi (Rubus chingii Hu) are most closely related, and then is blackberry (Rubus occidentalis). Further resequencing of 101 samples of Shanmei collected from four regions in provinces of Yunnan, Hunan, Jiangxi, and Sichuan in South China reveals that the Hunan population of Shanmei possesses the highest diversity and may represent the relatively more ancestral population. Moreover, the Yunnan population undergoes strong selection based on nucleotide diversity, linkage disequilibrium, and the historical effective population size analyses. Furthermore, genes from candidate genomic regions that show strong divergence are significantly enriched in flavonoid biosynthesis and plant hormone signal transduction, indicating the genetic basis of adaptation of Shanmei to the local environments. The high-quality genome sequences and the variome dataset of Shanmei provide valuable resources for breeding applications and for elucidating the genome evolution and ecological adaptation of Rubus species.

Muscle satellite cells (SCs) are responsible for muscle homeostasis and regeneration; and lncRNAs play important roles in regulating SC activities. Here in this study, we identify PAM-1 (Pax7 Associated Muscle lncRNA) that is induced in activated SCs to promote SC activation into myoblast cells upon injury. PAM-1 is generated from a myoblast specific super-enhancer (SE); as a seRNA it binds with a number of target genomic loci predominantly in trans. Further studies demonstrate that it interacts with Ddx5 to tether PAM-1 SE to it inter-chromosomal targets Timp2 and Vim to activate the gene expression. Lastly, we show that PAM-1 expression is increased in aging SCs, which leads to enhanced inter-chromosomal interaction and target genes up-regulation. Altogether, our findings identify PAM-1 as a previously unknown lncRNA that regulates both SC activation and aging through its trans gene regulatory activity.

Rubus corchorifolius ("Shanmei" or mountain berry, 2n = 14) is widely distributed in China, and its fruit has high nutritional and medicinal value. Here, we report a high-quality chromosome-scale genome assembly of Shanmei, with a size of 215.69 Mb and encompassing 26,696 genes. Genome comparisons among Rosaceae species showed that Shanmei and Fupenzi (Rubus chingii Hu) were most closely related, followed by blackberry (Rubus occidentalis), and that environmental adaptation-related genes were significantly expanded in the Shanmei genome. Further resequencing of 101 samples of Shanmei collected from four regions in the provinces of Yunnan, Hunan, Jiangxi, and Sichuan in China revealed that the Hunan population of Shanmei possessed the highest diversity and represented the more ancestral population. Moreover, the Yunnan population underwent strong selection based on nucleotide diversity, linkage disequilibrium, and the historical effective population size analyses. Furthermore, genes from candidate genomic regions that showed strong divergence were significantly enriched in flavonoid biosynthesis and plant hormone signal transduction, indicating the genetic basis of adaptation of Shanmei to the local environment. The high-quality genome sequences and the variome dataset of Shanmei provide valuable resources for breeding applications and for elucidating the genome evolution and ecological adaptation of Rubus species.

Long non-coding RNAs (lncRNAs) are key regulators of major biological processes and their functional modes are dictated by their subcellular localization. Relative nuclear enrichment of lncRNAs compared to mRNAs is a prevalent phenomenon but the molecular mechanisms governing their nuclear retention in cells remain largely unknown. Here in this study, we harness the recently released eCLIP data for a large number of RNA-binding proteins (RBPs) in K562 and HepG2 cells and utilize multiple bioinformatics methods to comprehensively survey the roles of RBPs in lncRNA nuclear retention. We identify an array of splicing RBPs that bind to nuclear-enriched lincRNAs (large intergenic non-coding RNAs) thus may act as trans-factors regulating their nuclear retention. Further analyses reveal that these RBPs may bind with distinct core motifs, flanking sequence compositions, or secondary structures to drive lincRNA nuclear retention. Moreover, network analyses uncover potential co-regulatory RBP clusters and the physical interaction between HNRNPU and SAFB2 proteins in K562 cells is further experimentally verified. Altogether, our analyses reveal previously unknown factors and mechanisms that govern lincRNA nuclear localization in cells.

Tet dioxygenases are responsible for the active DNA demethylation. The functions of Tet proteins in muscle regeneration have not been well characterized. Here we find that Tet2, but not Tet1 and Tet3, is specifically required for muscle regeneration in vivo. Loss of Tet2 leads to severe muscle regeneration defects. Further analysis indicates that Tet2 regulates myoblast differentiation and fusion. Tet2 activates transcription of the key differentiation modulator Myogenin (MyoG) by actively demethylating its enhancer region. Re-expressing of MyoG in Tet2 KO myoblasts rescues the differentiation and fusion defects. Further mechanistic analysis reveals that Tet2 enhances MyoD binding by demethylating the flanking CpG sites of E boxes to facilitate the recruitment of active histone modifications and increase chromatin accessibility and activate its transcription. These findings shed new lights on DNA methylation and pioneer transcription factor activity regulation.

Epigenetic alterations occur in various cells and tissues during aging, but it is not known if such alterations are also associated with aging in skeletal muscle. Here, we examined the changes of a panel of histone modifications and found H3K27ac (an active enhancer mark) is markedly increased in aged human skeletal muscle tissues. Further analyses uncovered that the H3K27ac increase and enhancer activation are associated with the up‐regulation of extracellular matrix (ECM) genes; this may result in alteration of the niche environment for skeletal muscle stem cells, also called satellite cells (SCs), which causes decreased myogenic potential and fibrogenic conversion of SCs. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation, inhibited the ECM up‐regulation and fibrogenic conversion of SCs and restored their myogenic differentiation potential. Altogether, our findings not only uncovered a novel aspect of skeletal muscle aging that is associated with enhancer remodeling but also implicated JQ1 as a potential treatment approach for restoring SC function in aging muscle.

Motivation Thousands of long noncoding RNAs (lncRNAs) were newly identified from high throughput RNA-seq data. Functional annotation and prioritization of these lncRNAs for further experimental validation as well as the functional investigation is the bottleneck step for many noncoding RNA studies. Results Here we describe lncFunTK that can run either as standard application or webserver for this purpose. It integrates high throughput sequencing data (i.e. ChIP-seq, CLIP-seq and RNA-seq) to construct the regulatory network associated with lncRNAs. Through the network, it calculates the Functional Information Score (FIS) of each individual lncRNA for prioritizing and inferring its functions through Gene Ontology (GO) terms of neighboring genes. In addition, it also provides utility scripts to support the input data preprocessing and the parameter optimizing. We further demonstrate that lncFunTK can be widely used in various biological systems for lncRNA prioritization and functional annotation. Availability and implementation The lncFunTK standalone version is an open source package and freely available at http://sunlab.cpy.cuhk.edu.hk/lncfuntk under the MIT license. A webserver implementation is also available at http://sunlab.cpy.cuhk.edu.hk/lncfuntk/runlncfuntk.html. Supplementary information Supplementary data are available at Bioinformatics online.

Natural antibodies have been found to have anti-tumorigenic function. This study was designed to investigate whether natural IgG antibodies against vascular endothelial growth factor receptor 1 (VEGFR1) could suppress the growth of hepatocellular carcinoma (HCC) cells. Three HCC cell lines and A549 lung cancer cells were used for this study. They were grown, respectively, with human plasma positive or negative for anti-VEGFR1 IgG. Cell viability, apoptosis and VEGFR1 gene expression were examined. Three patients with HCC were recruited for a case study. The results showed that plasma anti-VEGFR1 IgG significantly inhibited the proliferation of all three HCC cell lines but not A549 cell line; the proportions of apoptotic cells were significantly higher in HCC cells treated with anti-VEGFR1 IgG positive plasma than those treated with IgG negative plasma. The expression of the VEGFR1 gene was significantly higher in HCC cells than A549 cells. Of three HCC patients who received transfusion of anti-VEGFR1 IgG positive plasma, two cases with stage B showed a good response to the treatment but one with distant metastasis did not. Human plasma IgG against VEGFR1 may be a promising agent for anti-HCC therapy.

Our recent work demonstrated that circulating levels of IgG antibody to linear peptide antigens derived from annexin A1 (ANXA1) were significantly increased in lung cancer. The present study was then undertaken to test whether circulating anti-ANXA1 antibodies were also altered in breast cancer. An enzyme-linked immunosorbent assay was developed in-house to determine circulating IgG against ANXA1-derived peptide antigens in 152 female patients with breast cancer and 160 female control subjects. Student’s t test revealed that patients with breast cancer had significantly higher levels of anti-ANXA1 IgG than control subjects (t = 4.75, P

Overexpression of the p16 protein has been reported in breast cancer and may trigger the secretion of antibodies against itself. Circulating anti-p16 antibodies that were detected with a recombinant protein have been reported in breast cancer. The present study was designed to determine whether the levels of circulating IgG antibody to p16 protein-derived linear antigens are altered in breast cancer. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to determine circulating IgG against peptide antigens derived from the p16 protein in 152 female breast cancer patients and 160 healthy female subjects. The Student's T-test revealed that breast cancer patients exhibited significantly higher levels of anti-p16 IgG antibody compared to control subjects (T=2.02, P=0.045). In addition, ductal cancer appeared to be the main type contributing to the increased levels of circulating anti-p16 antibodies (T=2.08, P=0.038). Of all four stages of breast cancer, stage I was associated with the highest levels of IgG antibody (T=2.02, P=0.045) and receiver operating characteristic (ROC) analysis demonstrated that the area under the ROC curve was 0.74 (95% confidence interval: 0.65–083) and that the sensitivity against a specificity of 90% was 30.3%. Therefore, the levels of circulating IgG antibody to the p16 protein may be a potential biomarker for early diagnosis of breast cancer.

This research is based on the analysis of an origin-destination survey of users of Central Florida's expressway system. It presents an initial investigation of the drivers' choice in accessing/exiting the ramps of the system. The implications for route choice and spatial behavior are also addressed. The results showed that the distance traveled to access or after exiting a ramp does not depend only on the spacing between ramps, but on several factors, such as the trip purpose, vehicle occupancy, driver's income level, and E-Pass use [whether the vehicle is equipped with an electronic toll collection system (ETC)]. A significant result also was that there is considerable difference in the drivers' choices between entering and exiting the expressway. There is an indication that drivers prefer to access the expressway at shorter distances from their origins, but they are willing to travel longer distances to their destinations once they exit the expressway. A simplistic route choice analysis also presents some insights into the route choice paradigm. Route choice was found to be a function of several factors including the travel time, toll cost, and simplicity of the route (represented by the number of different roadway segments). The existence of a guide sign directing the driver to his/her destination also had an important impact on route choice, particularly for nonfamiliar travelers. Another factor, specific to toll roads, is the toll payment facility and toll payment method. Drivers of vehicles equipped with the ETC system (E-Pass), in a certain scenario, preferred a different route from drivers with no E-Pass. Finally, a multinomial logit route choice model was developed and illustrated the significance of several factors including the direction of travel, frequency of making the trip, age, residency, and E-Pass use on the likelihood of choosing a certain route. This research confirmed findings from previous work and the literature that route choice is a function of multiple factors and not only travel time or distance.

To investigate the efficacy of endolymphatic sac surgery for Meniere's disease, and compare the effects of endolymphatic sac decompression with endolymphatic-mastoid shunting.Twelve patients(13 ears) undergoing endolymphatic-mastoid shunting and eleven patients (11 ears) undergoing endolymphatic sac decompression were retrospectively compared for hearing results and vertigo controlled rates. All of them have been followed up for more than two years after surgery.According to Chinese Meniere's disease diagnosis and curative effect standard evaluation criteria published in 2006, for vertigo symptom of endolymphatic mastoid shunting group, 9 cases (69.2%) achieved grade A(completely controlled), 4 cases (30.8%) achieved grade B (fundamentally controlled). There were 8 cases (72.7%) with grade A, 2 cases (18.2%) with grade B and one case (9%) with grade C among 11 patients who received endolymphatic sac decompression. There was not statistically significant differences in postoperative speech pure tone average and vertigo controlled rate between the two groups.Endolymphatic sac decompression and endolymphatic-mastoid shunting are effective management with less complication for intractable Meniere's disease. Particularly, the vertigo symptoms were controlled significantly. Patients with Meniere's disease in advanced clinical stages may also be relieved.

To study the feasibility and clinical values of occupational noise-induced hearing loss measured, evaluated and diagnosed with transient evoked otoacoustic emissions (TEOAE).Pure tone threshold and TEOAE were performed in 11 (22 ears) young adults with normal hearing of control group and 90 (180 ears) noise exposure workers of test group. According to length of noise exposure time, test group was disparted to test 1,2,3 groups. Stimulated tone of TEOAE is non-linearity click of 80 dB SPL.In test group and test 1,2,3 group against control, pure tone threshold in all frequency increased significantly, and correlation, strength and SNR of TEOAE in overall and every frequency declined significantly (P0.05 or P0.01). To observe test 1,2,3 group, It was found that pure tone threshold in all frequency increased and correlation, strength and SNR of TEOAE in overall and every frequency declined, when length of noise exposure time is increased. In 2.50-3.50 and 3.50-4.50 kHz, measuring values of TEOAE declined most significantly.Occupational noise-induced hearing loss can been measured and diagnosed significantly with TEOAE. The best observed contents is correlation, strength and SNR of TEOAE in overall and every part frequency. The best sensitivity observed frequency parts of TEOAE is 2.50-3.50 and 3.50-4.50 kHz.

To determine the threshold of multiple auditory steady-state evoked responses(ASSR) of young adults with normal hearing, and to offer essential diagnosticate datas.ASSR were examined in 22 (44 ears) young adults with normal hearing. There were 11 men and 11 women in 22 young adults.Average threshold of ASSR were about 40 to 60 dBHL between 0.25-8.0 kHz, and they became higher from low frequency to high frequency. Average threshold of MFSSR were 40 dBHL at 0.25-0.5, 1 kHz, and about 45 dB HL at 2 kHz, and about 50 dB HL at 4 kHz, and about 60 dB HL at 8 kHz. Difference values were about 25 to 55 dB HL between average threshold values of ASSR and hearing, and they became higher from low frequency to high frequency, those were about 25 dBHL at 0.25 kHz, about 30 dBHL at 0.5 kHz, about 35 dBHL at 1 kHz, about 40 dB HL at 2 kHz, about 50 dB HL at 4 kHz, about 55 dBHL at 8 kHz.There is a definite numeral value between threshold of ASSR and hearing in young adults with normal hearing. Pure tone hearing threshold can be conferred by examining the threshold of ASSR and by using the definite numeral values.

To study the role of platelet activating factor (PAF) in the pathogenesis of secretory otitis media (SOM).The content of PAF in blood plasma and middle ear effusion(MEE) were measured in 56(68years) patients with secretory otitis media and in 40 normal subjects respectively by RP-HPLC.The concentration of PAF in MEE was remarkably higher than those in blood plasma (P0.01). The concentration of PAF in blood plasma in the SOM group was higher than those in the normal control group(P0.05). The concentration of PAF of MEE in the mucous fluid group was higher than those in the serous fluid group(P0.01).PAF might be an important mediator in MEE of SOM, it might be closely related to the persistence of SOM, and might play an important role in the pathogenesis of SOM.

To study the clinical characteristics and outline of surgery for carotid body tumor and glomus jugular tumor.Incisions of anterior border of sterno-mastoid muscle was made for simple carotid body tumor. A big S shape incisions and infratemporal fossa approach were employed which exposure the jugular foramen and apex of petrous for glomus jugular tumor or suffered carotid body tumor and glomus jugular tumor simultaneously in same side.Five cases of carotid body tumor were removed thoroughly and the internal carotid artery were intact reserved. In 5 cases of glomus jugular tumor 3 cases were removed thoroughly, other 2 cases of glomus jugular tumor were palliative operation, the remnant tumor have not increased in size after 1 to 3 years follow up.Chemodectoma have some genetic characteristic. Surgical intervention is the cardinal method of treatment.