Metabolic Pathways Enhancement Confers Poor Prognosis in p53 Exon Mutant Hepatocellular Carcinoma.

RNA-Sequencing (RNA-Seq), the most commonly used sequencing application tool, is not only a method for measuring gene expression but also an excellent media to detect important structural variants such as single nucleotide variants (SNVs), insertion/deletion (Indels), or fusion transcripts. The Cancer Genome Atlas (TCGA) contains genomic data from a variety of cancer types and also provides the raw data generated by TCGA consortium. p53 is among the top 10 somatic mutations associated with hepatocellular carcinoma (HCC). The aim of the present study was to analyze concordant different gene profiles and the priori defined set of genes based on p53 mutation status in HCC using RNA-Seq data. In the study, expression profile of 11 799 genes on 42 paired tumor and adjacent normal tissues was collected, processed, and further stratified by the mutated versus normal p53 expression. Furthermore, we used a knowledge-based approach Gene Set Enrichment Analysis (GSEA) to compare between normal and p53 mutation gene expression profiles. The statistical significance (nominal P value) of the enrichment score (ES) genes was calculated. The ranked gene list that reflects differential expression between p53 wild-type and mutant genotypes was then mapped to metabolic process by KEGG, an encyclopedia of genes and genomes to assign functional meanings. These approaches enable us to identify pathways and potential target gene/pathways that are highly expressed in p53 mutated HCC. Our analysis revealed 2 genes, the hexokinase 2 (HK2) and Enolase 1 (ENO1), were conspicuous of red pixel in the heatmap. To further explore the role of these genes in HCC, the overall survival plots by Kaplan-Meier method were performed for HK2 and ENO1 that revealed high HK2 and ENO1 expression in patients with HCC have poor prognosis. These results suggested that these glycolysis genes are associated with mutated-p53 in HCC that may contribute to poor prognosis. In this proof-of-concept study, we proposed an approach for identifying novel potential therapeutic targets in human HCC with mutated p53. These approaches can take advantage of the massive next-generation sequencing (NGS) data generated worldwide and make more out of it by exploring new potential therapeutic targets

Design and Development of Novel Electroplating Spring Frame Mems Structure Specimens for the Microtensile Testing of Thin Film Materials

Microelectromechanical systems (MEMS) technologies are developing rapidly with increasing study of the design, fabrication and commercialization of microscale systems and devices. Accurate mechanical properties are important for successful design and development of MEMS. We have demonstrated here a novel electroplating spring frame MEMS Structure Specimen integrates pin-pin align holes, misalignment compensate spring structure frame, load sensor beam and freestanding thin film. The specimen can be fit into a specially designed microtensile apparatus which is capable of carrying out a series of tests on sub-micro scale freestanding thin films.Comment: Submitted on behalf of TIMA Editions (http://irevues.inist.fr/tima-editions

Perforated Appendiceal Mucinous Cystadenoma Mimicking Ruptured Appendicitis With Abscess Formation: CT Imaging Features

AbstractWe describe the imaging features of a perforated appendiceal mucinous cystadenoma in a 72-year-old woman presenting with right lower quadrant abdominal pain, mimicking ruptured appendicitis with abscess formation. Computed tomography revealed a rim-enhanced cystic lesion at the proximal appendiceal orifice, connecting with the swollen and dilated distal part of the appendix. Disruption of the appendiceal walls and peri-appendiceal fatty infiltrations were also noted. Under the impression of ruptured appendicitis with abscess formation, the patient underwent exploratory laparotomy and appendectomy. The pathologic diagnosis was perforated appendiceal mucinous cystadenoma associated with superinfection, complicated by secondary appendicitis. The patient was uneventfully discharged on the 7th hospital day. Although primary neoplasms of the appendix are uncommon, they should be considered as a predisposing factor in elderly patients manifesting with appendicitis

Ringtone Regardless of P-Early-Media Tag

A user device placing a mobile originating call on a network using Real-time Transport Protocol (RTP) ignores P-Early-Media tags and session description protocol (SDP) in Session Initiation Protocol (SIP) packets received from the network after receiving a 180 Ringing alert packet indicating that the receiving device is ringing to minimize a delay in playing a ringback tone. The user device plays a local ringtone until the user device receives audio RTP packets containing Early Media. If the user device receives audio RTP packets containing Early Media before the call is connected, the user device plays the Early Media as a custom ringtone

Antagonism between abscisic acid and ethylene in Arabidopsis acts in parallel with the reciprocal regulation of their metabolism and signaling pathways

Although abscisic acid (ABA) and ethylene have antagonistic functions in the control of plant growth and development, including seed germination and early seedling development, it remains unknown whether a convergent point exists between these two signaling pathways or whether they operate in parallel in Arabidopsis thaliana. To elucidate this issue, four ethylene mutants, ctr1, ein2, ein3, and ein6, were crossed with aba2 (also known as gin1-3) to generate double mutants. Genetic epistasis analysis revealed that all of the resulting double mutants displayed aba2 mutant phenotypes with a small plant size and wiltiness when grown in soil or on agar plates. Further ethylene sensitivity or triple response analyses demonstrated that these double mutants also retained the ctr1 or ein mutant phenotypes, showing ethylene constitutive triple and insensitive responses, respectively. Our current data therefore demonstrate that ABA and ethylene act in parallel, at least in primary signal transduction pathways. Moreover, by microarray analysis we found that an ACC oxidase (ACO) was significantly upregulated in the aba2 mutant, whereas the 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3) gene in ein2 was upregulated, and both the ABSCISIC ACID INSENSITIVE1 (ABI1) and cytochromeP450, family 707, subfamily A, polypeptide 2 (CYP707A2) genes in etr1-1 were downregulated. These data further suggest that ABA and ethylene may control the hormonal biosynthesis, catabolism, or signaling of each other to enhance their antagonistic effects upon seed germination and early seedling growth

Crystallization of Adenylylsulfate Reductase from Desulfovibrio gigas: A Strategy Based on Controlled Protein Oligomerization

Adenylylsulfate reductase (adenosine 5′-phosphosulfate reductase, APS reductase or APSR, E.C.1.8.99.2) catalyzes the conversion of APS to sulfite in dissimilatory sulfate reduction. APSR was isolated and purified directly from massive anaerobically grown Desulfovibrio gigas, a strict anaerobe, for structure and function investigation. Oligomerization of APSR to form dimers–α_2β_2, tetramers–α_4β_4, hexamers–α_6β_6, and larger oligomers was observed during purification of the protein. Dynamic light scattering and ultracentrifugation revealed that the addition of adenosine monophosphate (AMP) or adenosine 5′-phosphosulfate (APS) disrupts the oligomerization, indicating that AMP or APS binding to the APSR dissociates the inactive hexamers into functional dimers. Treatment of APSR with β-mercaptoethanol decreased the enzyme size from a hexamer to a dimer, probably by disrupting the disulfide Cys156—Cys162 toward the C-terminus of the β-subunit. Alignment of the APSR sequences from D. gigas and A. fulgidus revealed the largest differences in this region of the β-subunit, with the D. gigas APSR containing 16 additional amino acids with the Cys156—Cys162 disulfide. Studies in a pH gradient showed that the diameter of the APSR decreased progressively with acidic pH. To crystallize the APSR for structure determination, we optimized conditions to generate a homogeneous and stable form of APSR by combining dynamic light scattering, ultracentrifugation, and electron paramagnetic resonance methods to analyze the various oligomeric states of the enzyme in varied environments

Aging-Induced Dynamics for Statically Indeterminate System

Statically indeterminate systems are experimentally demonstrated to be in fact dynamical at the microscopic scale. Take the classic ladder-wall problem, for instance. Depending on the Young's modulus of the wall, it may take up to twenty minutes before its weight saturates. This finding is shown to be shared by other statically indeterminate systems, such as a granule silo and a beam with three support points. We believe that the aging effect is responsible for this surprising phenomenon because it can be correlated with the evolution of microscopic contact area with the wall and floor. Finally, a heuristic and simple method is introduced that can uniquely determine and analytically solve the saturated weight without invoking detailed material properties.Comment: 5 pages, 5 figure

New primers for methylation-specific polymerase chain reaction enhance specificity of detecting STAT1 methylation

AbstractObjectiveSignal transducer and activator of transcription (STAT)1 is a key tumor suppressor, which is always methylated in a variety of human cancers. However, nonspecific primers for the detection of specific promoter hypermethylation of STAT1 gene can lead to false-positive or false-negative results for gene methylation.Materials and MethodsWe designed new primers for the detection of STAT1 methylation and compared the sensitivities and specificities of these new primers with prior published primers by methylation-specific polymerase chain reaction (PCR) from ovarian clear cell carcinomas. The mRNA expression levels of STAT1 in these cancerous tissues were also evaluated by reverse-transcriptase PCR and correlated with the results of promoter methylation of STAT1 gene.ResultsNine (39%) of the 23 samples detected by the new primers and 13 samples (56%) detected by prior published primers showed STAT1 methylation. A direct DNA sequencing test revealed that four of the 13 samples (30.8%) showed false positivity for STAT1 methylation using the prior published primers. In contrast, none of the nine samples was false-positive for the detection of STAT1 methylation using the new primers. The new primers for the detection of STAT1 methylation showed 100% specificity and 100% sensitivity without false positivity.ConclusionSpecific primers for methylation-specific PCR are mandatory for the accurate detection of STAT1 gene methylation. Besides, specific primers can generate correct interpretation of STAT1 gene methylation, and its correlation with the clinicopathological characteristics and outcome of cancer patients

HPV infection and p53 inactivation in pterygium

PurposeOur recent report indicated that tumor suppressor gene (p53) mutations and protein aberrant expression were detected in pterygium. Inactivation of p53 by Human papillomavirus (HPV) 16/18 E6 plays a crucial role in cervical tumorigenesis. In this study, we further speculate that p53 inactivation may be linked with HPV infection in pterygium pathogenesis. To investigate the involvement of HPV 16/18 E6 in p53 inactivation in pterygium, the association between HPV 16 or HPV 18 infection, the HPV E6 oncoprotein, and p53 protein expression was analyzed in this study.MethodsHPV 16/18 infection was detected by nested-polymerase chain reaction (nested-PCR), the p53 mutation was detected by direct sequencing, and the p53 and the HPV 16/18 E6 proteins were studied using immunohistochemistry on 129 pterygial specimens and 20 normal conjunctivas.ResultsThe HPV 16/18 was detected in 24% of the pterygium tissues (31 of 129) but not in the normal conjunctiva, and the HPV16/18 E6 oncoprotein was detected in 48.3% of HPV 16/18 DNA-positive pterygium tissues (15 of 31). In addition, p53 protein negative expression in pterygium was correlated with HPV16/18 E6 oncoprotein expression but not with a p53 mutation.ConclusionsHPV 16/18 E6 contributes to HPV-mediated pterygium pathogenesis as it is partly involved in p53 inactivation and is expressed in HPV DNA-positive pterygium