Summary
By integrating the multilevel biological evidence and bioinformatics analyses, the present study represents a systemic endeavor to identify BMD-associated genes and their roles in skeletal ...metabolism.
Introduction
Single-nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) have already identified about 100 loci associated with bone mineral density (BMD), but these loci only explain a small proportion of heritability to osteoporosis risk. In the present study, we performed a gene-based analysis of the largest GWASs in the bone field to identify additional BMD-associated genes.
Methods
BMD-associated genes were identified by combining the summary statistic
P
values of SNPs across individual genes in the two consecutive meta-analyses of GWASs from the Genetic Factors for Osteoporosis (GEFOS) studies. The potential functionality of these genes to bone was partially assessed by differential gene expression analysis. Additionally, the consistency of the identification of potential bone mineral density (BMD)-associated variants were evaluated by estimating the correlation of the
P
values of the same single-nucleotide polymorphisms (SNPs)/genes between the two consecutive Genetic Factors for Osteoporosis Studies (GEFOS) with largely overlapping samples.
Results
Compared to the SNP-based analysis, the gene-based strategy identified additional BMD-associated genes with genome-wide significance and increased their mutual replication between the two GEFOS datasets. Among these BMD-associated genes, three novel genes (
UBTF
,
AAAS
, and
C11orf58
) were partially validated at the gene expression level. The correlation analysis presented a moderately high between-study consistency of potential BMD-associated variants.
Conclusions
Gene-based analysis as a supplementary strategy to SNP-based genome-wide association studies, when applied here, is shown that it helped identify some novel BMD-associated genes. In addition to its empirically increased statistical power, gene-based analysis also provides a higher testing stability for identification of BMD genes.
The temporal resolution of ultrafast electron diffraction and microscopy experiments is currently limited by the available experimental techniques for the generation and characterization of electron ...bunches with single femtosecond or attosecond durations. Here, we present proof of principle experiments of an optical gating concept for free electrons via direct time-domain visualization of the sub-optical cycle energy and transverse momentum structure imprinted on the electron beam. We demonstrate a temporal resolution of 1.2±0.3 fs. The scheme is based on the synchronous interaction between electrons and the near-field mode of a dielectric nano-grating excited by a femtosecond laser pulse with an optical period duration of 6.5 fs. The sub-optical cycle resolution demonstrated here is promising for use in laser-driven streak cameras for attosecond temporal characterization of bunched particle beams as well as time-resolved experiments with free-electron beams.
Abstract The corona is a structure possessed by stars, including the Sun. The abnormal heating of the solar corona and chromosphere is one of the greatest mysteries in modern astronomy. While ...state-of-the-art observations have identified some candidates of magnetic activity events that could be responsible for this abnormal heating, and theoretical studies have proposed various heating modes, a complete physical picture of how they are heated as a whole remains elusive. In this study, the characteristics of the heated corona and chromosphere are investigated, and for the first time, the question of how they are abnormally heated is explicitly answered by analyzing the long-term observations of the global chromosphere in the Ca ii K line and the global corona in the coronal green line. The findings reveal that both the quiet chromosphere and corona are in antiphase with the solar cycle, whereas the active chromosphere and corona are in phase with it. Different parts of the solar corona and chromosphere exhibit significantly different variation characteristics and are found to be heated by different magnetic categories and probably in different modes. This study posits that unraveling the heating mystery is best approached through the lens of magnetic categories, rather than magnetic activity events.
▶ Fisheries can impact species, habitats and ecological communities. ▶ We describe a risk-based framework to assess these impacts. ▶ Novel features include a hierarchical structure and a ...precautionary approach. ▶ This framework has applicability in a wide range of fisheries.
Management of fisheries around the world is challenged by fishing impacts on habitats, bycatch species, threatened and endangered species, and even associated ecological communities. One response to these other factors has been a call for ecosystem-based fisheries management (EBFM), which demands consideration of the above non-target interactions. A challenge with implementation of EBFM is the scale and range of issues to be considered, all of which cannot be addressed at the same level of detail as for target species, due to data or time constraints. We developed an approach to progress the EBFM mandate in Australia, using a new ecological risk assessment framework applied to fisheries, termed Ecological Risk Assessment for the Effects of Fishing (ERAEF). Novel features of this framework include its hierarchical structure and its precautionary approach to uncertainty. The amount of information required increases through the hierarchy, and allows application in data-limited situations. The ERAEF framework has been applied to over 30 fisheries in Australia and elsewhere. The efficiencies in application of the hierarchical approach are illustrated by the south-east otter trawl fishery, where following Level 1 assessment of all components, an initial set of 600 species and 158 habitats was reduced to a group of concern of 159 species and 46 habitats using the Level 2 analysis, with the number of species of concern further reduced to 25 following Level 3 analysis. As a result of the assessments in Australia, management actions have been enacted for a range of the high risk species. Overall, the ERAEF approach offers a realistic method to assess ecological risk in an EBFM context, and has applicability in a wide range of fisheries. The interactive and inclusive nature of the approach also has the advantage of bringing stakeholders, scientists and managers together to develop management solutions.
Oncogenomic studies indicate that copy number variation (CNV) alters genes involved in tumor progression; however, identification of specific driver genes affected by CNV has been difficult, as these ...rearrangements are often contained in large chromosomal intervals among several bystander genes. Here, we addressed this problem and identified a CNV-targeted oncogene by performing comparative oncogenomics of human and zebrafish melanomas. We determined that the gene encoding growth differentiation factor 6 (GDF6), which is the ligand for the BMP family, is recurrently amplified and transcriptionally upregulated in melanoma. GDF6-induced BMP signaling maintained a trunk neural crest gene signature in melanomas. Additionally, GDF6 repressed the melanocyte differentiation gene MITF and the proapoptotic factor SOX9, thereby preventing differentiation, inhibiting cell death, and promoting tumor growth. GDF6 was specifically expressed in melanomas but not melanocytes. Moreover, GDF6 expression levels in melanomas were inversely correlated with patient survival. Our study has identified a fundamental role for GDF6 and BMP signaling in governing an embryonic cell gene signature to promote melanoma progression, thus providing potential opportunities for targeted therapy to treat GDF6-positive cancers.
Introduction
Seroma is a commonly encountered sequela after hernia repair. Tremendous effort has been spent to investigate the effective way to prevent this “complication” including the modification ...of surgical technique, use of per-peritoneal drainage, etc. There were debates about the use of monopolar diathermy versus blunt dissection in laparoscopic TEP in the prevention of seroma formation. This randomized study aims to compare the effects of using 2 techniques in laparoscopic TEP on pre-peritoneal drain output and seroma formation.
Method
From 1.9.2018 to 30.9.2019, all male and female patients presented with the first occurrence, unilateral inguinal hernia anticipated for laparoscopic TEP were enrolled into the study after informed consent. Patients were randomized into “monopolar dissection preferred” (MDP) group and “blunt dissection-preferred” (BDP) group just before commencing of operation after general anesthesia. Surgeons were instructed to use monopolar energy as main dissection method for the whole operation if possible (MDP), whereas blunt dissection is the preferred choice in BDP group, but the use of monopolar energy was allowed if needed. Total energy time was measured by a specially designed homemade device attaching to the monopolar pedals as accurate as to millisecond (ms). Pre-peritoneal drains were inserted for drainage and removed 23 h after operation. Drainage output, total operating time, energy time, clinical and ultrasonic seroma sizes at day 1, day 6, 1-month post operations, recurrence are compared between 2 groups.
Results
A total of 103 patients where included. There was no significant difference in age, gender, co-morbidities, side of hernia, mean defect size, operating time, fixation adjuncts, or postoperative stay. The drain volume in BDP group is 71.13 ± 31.42 mL while it in MDP group is 56.36 ± 21.46 mL. The MDP group had significantly fewer drain output at 23 h post operation (
p
= 0.007) and lower seroma incidence on days 6 (
p
= 0.036). Overall incidence of seroma formation was 12% on postoperative day 1, 11% on postoperative day 7. No statistically differences in postoperative pain score or complications were observed at the first week, 1- and 3-months’ post operation. There was no correlation with energy time to the drain output. No recurrence was found in subsequent follow-up.
Conclusion
Pre-peritoneal drainage is clinically safe in laparoscopic totally extra-peritoneal hernioplasty and can effectively reduce the size and incidence of seroma. The seroma formation can be further reduced by appropriate use of monopolar energy as preferred dissection approach in lap TEP. Due to limitation in measuring the actual energy time, the result should be further validated by randomized multi-centers trial on its potential benefit in hernia repair by a more accurate measuring device on energy used.
Predictive biomarkers for early diagnosis of prostate cancer are important for its treatment. The functional microRNAs in the exosomes of plasma and serum samples are of interest as stable and ...non-invasive biomarkers for recurrence in cancer patients. The present study aimed to clarify the value of plasma exosomal miRNA-125a-5p and miR-141-5p as biomarkers for the diagnosis of prostate cancer. The study included 19 healthy individuals and 31 prostate cancer patients. In comparison to the levels in healthy controls, exosomal miR-141-5p levels showed a slight increase in prostate cancer patients (p=0.085), and miR-125a-5p levels that showed a significant decrease in patients with prostate cancer than in healthy controls (p=0.032). As a derived parameter, the miR-125a-5p/miR-141-5p ratio was significantly higher in patients with prostate cancer than in healthy controls (p<0.001). We found that exosomal miR-141-5p in plasma showed a promise in distinguishing prostate cancer patients with the AUC of 0.652, and for miR-125a-5p, the AUC was 0.691. For the miR-125a-5p/miR-141-5p ratio, the AUC value was 0.793. We found that miR-125a-5p has a weak positive correlation with PSA (correlation coefficient = 0.3413). Moreover, miR-141-5p has been found to hold a negatively no-significant correlation with PSA, with the correlation coefficient is -0.1102. We speculate that, as diagnostic markers for prostate cancer, miR-125-5p and miR-141-5p might be independent of the PSA. In summary, the results of this study suggest that high plasma exosomal expression of miR-141-3p and low expression of miR-125a-5p in plasma exosomes from prostate cancer patients might be useful markers of specific tumor traits associated with prostate cancer. Moreover, the miR-125a-5p/miR-141-5p ratio seems to perform better than either of the single values alone.
Production of coal and natural gas is responsible for one third of anthropogenic methane (CH4) emissions in the United States. Here we examine CH4 emissions from coal and natural gas production in ...southwestern Pennsylvania. Using a top‐down methodology combining measurements of CH4 and ethane, we conclude that while Environmental Protection Agency inventories appear to report emissions from coal accurately, emissions from unconventional natural gas are underreported in the region by a factor of 5 (±3). However, production‐scaled CH4 emissions from unconventional gas production in the Marcellus remain small compared to other basins due to its large production per well. After normalizing emissions by energy produced, total greenhouse gas emissions from Pennsylvania unconventional natural gas production produce half the carbon footprint compared to regionally produced coal, with carbon dioxide emissions from combustion being the dominant source of greenhouse gas emissions for both sources.
Key Points
Methane and ethane observations from aircraft are used to quantify methane emissions from coal and natural gas production in Pennsylvania
Methane emissions from coal production align with national estimates, whereas emissions from natural gas production are underestimated
Energy produced through natural gas production in Pennsylvania has half the carbon footprint compared to energy from coal mining
Long non-coding RNAs (lncRNAs) CRNDE has been identified as a tumor oncogene in glioma. However, its clinical significance and prognostic value in glioma have not been investigated until now. The aim ...of this study was to explore CRNDE expression levels and evaluated its clinical significance in glioma patients.
Expression levels of lncRNA CRNDE in 164 glioma specimens were determined by quantitative real-time PCR (qRT-PCR). The chi-square test was used to explore CRNDE expression with respect to clinicopathological parameters. The overall survival was analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. Univariate and multivariate analyses were performed to analyze the prognostic significance of CRNDE expression.
Compared with nonneoplastic brain tissues, the expression level of CRNDE was significantly increased in glioma tissues (p < 0.01). CRNDE upregulation was correlated with larger tumor size (p = 0.011), higher WHO grade (p = 0.001), and recurrence (p = 0.008). Also, survival analysis proved that up-regulated CRNDE expression was associated with poor overall survival of glioma patients (p < 0.001). The multivariate Cox regression analysis indicated that CRNDE expression was an independent prognostic factor for overall survival.
These results indicated that lncRNA CRNDE was associated with tumor progression and could be an independent prognostic factor for glioma patients.
Abstract
A reference material used for the component analysis of high silica glass fiber is prepared by the high-temperature melting process, a technique that can ensure the homogeneity and stability ...of each component. With two methods based on different principles, the components in glass fiber are accurately characterized through the joint efforts of multiple laboratories. The results show that the reference material was accurately and reliably characterized and exhibited good homogeneity and stability, and that the expanded uncertainty of the standard values was 5%-10% (
k
=2). Therefore, the reference material can be used to evaluate component testing methods for high silica glass fiber and calibrate related analytical instruments so that the accuracy and reliability of component characterization are ensured.
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