Shotgun metagenome data of a defined mock community using Oxford Nanopore, PacBio and Illumina technologies.

Metagenomic sequence data from defined mock communities is crucial for the assessment of sequencing platform performance and downstream analyses, including assembly, binning and taxonomic assignment. We report a comparison of shotgun metagenome sequencing and assembly metrics of a defined microbial mock community using the Oxford Nanopore Technologies (ONT) MinION, PacBio and Illumina sequencing platforms. Our synthetic microbial community BMock12 consists of 12 bacterial strains with genome sizes spanning 3.2-7.2 Mbp, 40-73% GC content, and 1.5-7.3% repeats. Size selection of both PacBio and ONT sequencing libraries prior to sequencing was essential to yield comparable relative abundances of organisms among all sequencing technologies. While the Illumina-based metagenome assembly yielded good coverage with few misassemblies, contiguity was greatly improved by both, Illumina + ONT and Illumina + PacBio hybrid assemblies but increased misassemblies, most notably in genomes with high sequence similarity to each other. Our resulting datasets allow evaluation and benchmarking of bioinformatics software on Illumina, PacBio and ONT platforms in parallel

The regulatory and transcriptional landscape associated with carbon utilization in a filamentous fungus.

Filamentous fungi, such as Neurospora crassa, are very efficient in deconstructing plant biomass by the secretion of an arsenal of plant cell wall-degrading enzymes, by remodeling metabolism to accommodate production of secreted enzymes, and by enabling transport and intracellular utilization of plant biomass components. Although a number of enzymes and transcriptional regulators involved in plant biomass utilization have been identified, how filamentous fungi sense and integrate nutritional information encoded in the plant cell wall into a regulatory hierarchy for optimal utilization of complex carbon sources is not understood. Here, we performed transcriptional profiling of N. crassa on 40 different carbon sources, including plant biomass, to provide data on how fungi sense simple to complex carbohydrates. From these data, we identified regulatory factors in N. crassa and characterized one (PDR-2) associated with pectin utilization and one with pectin/hemicellulose utilization (ARA-1). Using in vitro DNA affinity purification sequencing (DAP-seq), we identified direct targets of transcription factors involved in regulating genes encoding plant cell wall-degrading enzymes. In particular, our data clarified the role of the transcription factor VIB-1 in the regulation of genes encoding plant cell wall-degrading enzymes and nutrient scavenging and revealed a major role of the carbon catabolite repressor CRE-1 in regulating the expression of major facilitator transporter genes. These data contribute to a more complete understanding of cross talk between transcription factors and their target genes, which are involved in regulating nutrient sensing and plant biomass utilization on a global level

Neurofilament Heavy Polypeptide Regulates the Akt-β-Catenin Pathway in Human Esophageal Squamous Cell Carcinoma

Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. We observed promoter methylation and loss of expression in neurofilament heavy polypeptide (NEFH) in a significant proportion of primary esophageal squamous cell carcinoma (ESCC) samples that were of a high tumor grade and advanced stage. RNA interference-mediated knockdown of NEFH accelerated ESCC cell growth in culture and increased tumorigenicity in vivo, whereas forced expression of NEFH significantly inhibited cell growth and colony formation. Loss of NEFH caused up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase, via activation of the Akt/β-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. The acceleration of glycolysis and mitochondrial dysfunction in NEFH-knockdown cells was suppressed in the absence of β-catenin expression, and was decreased by the treatment of 2-Deoxyglucose, a glycolytic inhibitor, or API-2, an Akt inhibitor. Loss of NEFH activates the Akt/β-catenin pathway and increases glycolysis and mitochondrial dysfunction. Cancer cells with methylated NEFH can be targeted for destruction with specific inhibitors of deregulated downstream pathways

SEGUE-2 Limits on Metal-Rich Old-Population Hypervelocity Stars In the Galactic Halo

We present new limits on the ejection of metal-rich old-population hypervelocity stars from the Galactic center (GC) as probed by the SEGUE-2 survey. Our limits are a factor of 3-10 more stringent than previously reported, depending on stellar type. Compared to the known population of B-star ejectees, there can be no more than 30 times more metal-rich old-population F/G stars ejected from the GC. Because B stars comprise a tiny fraction of a normal stellar population, this places significant limits on a combination of the GC mass function and the ejection mechanism for hypervelocity stars. In the presence of a normal GC mass function, our results require an ejection mechanism that is about 5.5 times more efficient at ejecting B-stars compared to low-mass F/G stars.Comment: 18 pages including 5 figures; Submitted to Ap

Old-Population Hypervelocity Stars from the Galactic Center: Limits from the SDSS

We present limits on the ejection of old-population HVS from a sample of over 290,000 stars selected from the SDSS. We derive the speed at the solar circle from the measured positions and radial velocities by assuming a radial orbit and adopting a simple isothermal model of the Galactic halo, which enables us to identify candidate bound and unbound ejectees. We find 4 candidate bound F-stars from this sample, all with negative Galactocentric radial velocity (i.e., returning toward the GC). We additionally find 2 candidate unbound stars (one F and one G), however, existing proper motion measurements make these unlikely to be emerging from the GC. These data place an upper limit on the rate of ejection of old-population stars from the GC of ~45/Myr. Comparing to the rate for more massive B-star ejectees of ~0.5/Myr, our limit on the rate of ejection of old-population HVS shows that the mass function at the GC is not bottom-heavy and is consistent with being normal. Future targeted surveys of old-population HVS could determine if it is indeed top-heavy.Comment: Submitted to ApJ; 14 pages including 2 figure

ssDNA-binding protein 2 is frequently hypermethylated and suppresses cell growth in human prostate cancer

Purpose: Prostate cancer is a major cause of cancer death among men and the development of new biomarkers is important to augment current detection approaches. Experimental Design: We identified hypermethylation of the ssDNA-binding protein 2 (SSBP2) promoter as a potential DNA marker for human prostate cancer based on previous bioinformatics results and pharmacologic unmasking microarray. We then did quantitative methylation-specific PCR in primary prostate cancer tissues to confirm hypermethylation of the SSBP2 promoter, and analyzed its correlation with clinicopathologic data. We further examined SSBP2 expression in primary prostate cancer and studied its role in cell growth. Results: Quantitative methylation-specific PCR results showed that the SSBP2 promoter was hypermethylated in 54 of 88 (61.4%) primary prostate cancers versus 0 of 23 (0%) in benign prostatic hyperplasia using a cutoff value of 120. Furthermore, we found that expression of SSBP2 was down-regulated in primary prostate cancers and cancer cell lines. Hypermethylation of the SSBP2 promoter and its expression were closely associated with higher stages of prostate cancer. Reactivation of SSBP2 expression by the demethylating agent 5-aza-2'-deoxycytidine in prostate cancer cell lines confirmed epigenetic inactivation as one major mechanism of SSBP2 regulation. Moreover, forced expression of SSBP2 inhibited prostate cancer cell proliferation in the colony formation assay and caused cell cycle arrest. Conclusion: SSBP2 inhibits prostate cancer cell proliferation and seems to represent a novel prostate cancer - specific DNA marker, especially in high stages of human prostate cancer

TOI-150: A transiting hot Jupiter in the TESS southern CVZ

We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J}$,$R_{p}=1.38\pm0.04\ R_{J}$) orbiting a middle-aged star ($\log g=4.152^{+0.030}_{-0.043}$) in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone ($\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ

Spectroscopic Mass and Host-star Metallicity Measurements for Newly Discovered Microlensing Planet OGLE-2018-BLG-0740Lb

We report the discovery of the microlensing planet OGLE-2018-BLG-0740Lb. The planet is detected with a very strong signal of $\Delta\chi^2\sim 4630$, but the interpretation of the signal suffers from two types of degeneracies. One type is caused by the previously known close/wide degeneracy, and the other is caused by an ambiguity between two solutions, in which one solution requires to incorporate finite-source effects, while the other solution is consistent with a point-source interpretation. Although difficult to be firmly resolved based on only the photometric data, the degeneracy is resolved in strong favor of the point-source solution with the additional external information obtained from astrometric and spectroscopic observations. The small astrometric offset between the source and baseline object supports that the blend is the lens and this interpretation is further secured by the consistency of the spectroscopic distance estimate of the blend with the lensing parameters of the point-source solution. The estimated mass of the host is $1.0\pm 0.1~M_\odot$ and the mass of the planet is $4.5\pm 0.6~M_{\rm J}$ (close solution) or $4.8\pm 0.6~M_{\rm J}$ (wide solution) and the lens is located at a distance of $3.2\pm 0.5$~kpc. The bright nature of the lens, with $I\sim 17.1$ ($V\sim 18.2$), combined with its dominance of the observed flux suggest that radial-velocity (RV) follow-up observations of the lens can be done using high-resolution spectrometers mounted on large telescopes, e.g., VLT/ESPRESSO, and this can potentially not only measure the period and eccentricity of the planet but also probe for close-in planets. We estimate that the expected RV amplitude would be $\sim 60\sin i ~{\rm m~s}^{-1}$.Comment: 12 pages, 11 figures, 4 table

Human AQP5 Plays a Role in the Progression of Chronic Myelogenous Leukemia (CML)

Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib mesylate resistance in paired samples (p = 0.047). We have found that the overexpression of AQP5 in K562 cells resulted in increased cell proliferation. In addition, small interfering RNA (siRNA) targeting AQP5 reduced the cell proliferation rate in both K562 and LAMA84 CML cells. Moreover, by immunoblotting and flow cytometry, we show that phosphorylation of BCR-ABL1 is increased in AQP5-overexpressing CML cells and decreased in AQP5 siRNA-treated CML cells. Interestingly, caspase9 activity increased in AQP5 siRNA-treated cells. Finally, FISH showed no evidence of AQP5 gene amplification in CML from bone marrow. In summary, we report for the first time that AQP5 is overexpressed in CML cells and plays a role in promoting cell proliferation and inhibiting apoptosis. Furthermore, our findings may provide the basis for a novel CML therapy targeting AQP5