ALMA twenty-six arcmin2 survey of GOODS-S at one millimeter (ASAGAO): Millimeter properties of stellar mass selected galaxies

We make use of the ASAGAO, deep 1.2 mm continuum observations of a 26 arcmin$^2$ region in the GOODS-South field obtained with ALMA, to probe dust-enshrouded star formation in $K$-band selected (i.e., stellar mass selected) galaxies, which are drawn from the ZFOURGE catalog. Based on the ASAGAO combined map, which was created by combining ASAGAO and ALMA archival data in the GOODS-South field, we find that 24 ZFOURGE sources have 1.2 mm counterparts with a signal-to-noise ratio $>$ 4.5 (1$\sigma\simeq$ 30 - 70 $\mu$Jy beam$^{-1}$ at 1.2 mm). Their median redshift is estimated to be $z_\mathrm{median}=$ 2.38 $\pm$ 0.14. They generally follow the tight relationship of the stellar mass versus star formation rate (i.e., the main sequence of star-forming galaxies). ALMA-detected ZFOURGE sources exhibit systematically larger infrared (IR) excess (IRX $\equiv L_\mathrm{IR}/L_\mathrm{UV}$) compared to ZFOURGE galaxies without ALMA detections even though they have similar redshifts, stellar masses, and star formation rates. This implies the consensus stellar-mass versus IRX relation, which is known to be tight among rest-frame-UV-selected galaxies, can not fully predict the ALMA detectability of stellar-mass-selected galaxies. We find that ALMA-detected ZFOURGE sources are the main contributors to the cosmic IR star formation rate density at $z$ = 2 - 3.Comment: Accepted for publication in PASJ. A version with a high resolution figure and ALMA fits files are available from https://sites.google.com/view/asagao26

ALMA deep field in SSA22: Blindly detected CO emitters and [C ii] emitter candidates

We report the identification of four millimeter line-emitting galaxies with the Atacama Large Milli/submillimeter Array (ALMA) in SSA22 Field (ADF22). We analyze the ALMA 1.1-mm survey data, with an effective survey area of 5 arcmin2, frequency ranges of 253.1–256.8 and 269.1–272.8 GHz, angular resolution of 0 ′′. .′′ 7 and rms noise of 0.8 mJy beam−1 at 36 km s−1 velocity resolution. We detect four line-emitter candidates with significance levels above 6σ. We identify one of the four sources as a CO(9–8) emitter at z = 3.1 in a member of the proto-cluster known in this field. Another line emitter with an optical counterpart is likely a CO(4–3) emitter at z = 0.7. The other two sources without any millimeter continuum or optical/near-infrared counterpart are likely to be [C II] emitter candidates at z = 6.0 and 6.5. The equivalent widths of the [C II] candidates are consistent with those of confirmed high-redshift [C II] emitters and candidates, and are a factor of 10 times larger than that of the CO(9–8) emitter detected in this search. The [C II] luminosity of the candidates are 4–7 × 108 L⊙. The star formation rates (SFRs) of these sources are estimated to be 10–20 M⊙ yr−1 if we adopt an empirical [C II] luminosity–SFR relation. One of them has a relatively low S/N ratio, but shows features characteristic of emission lines. Assuming that at least one of the two candidates is a [C II] emitter, we derive a lower limit of [C II]-based star formation rate density (SFRD) at z ∼ 6. The resulting value of >10−2 M⊙ yr−1 Mpc−3 is consistent with the dust-uncorrected UV-based SFRD. Future millimeter/submillimeter surveys can be used to detect a number of high-redshift line emitters, with which to study the star formation history in the early universe

Inhibition of Fried Meat-Induced Colorectal DNA Damage and Altered Systemic Genotoxicity in Humans by Crucifera, Chlorophyllin, and Yogurt

Dietary exposures implicated as reducing or causing risk for colorectal cancer may reduce or cause DNA damage in colon tissue; however, no one has assessed this hypothesis directly in humans. Thus, we enrolled 16 healthy volunteers in a 4-week controlled feeding study where 8 subjects were randomly assigned to dietary regimens containing meat cooked at either low (100°C) or high temperature (250°C), each for 2 weeks in a crossover design. The other 8 subjects were randomly assigned to dietary regimens containing the high-temperature meat diet alone or in combination with 3 putative mutagen inhibitors: cruciferous vegetables, yogurt, and chlorophyllin tablets, also in a crossover design. Subjects were nonsmokers, at least 18 years old, and not currently taking prescription drugs or antibiotics. We used the Salmonella assay to analyze the meat, urine, and feces for mutagenicity, and the comet assay to analyze rectal biopsies and peripheral blood lymphocytes for DNA damage. Low-temperature meat had undetectable levels of heterocyclic amines (HCAs) and was not mutagenic, whereas high-temperature meat had high HCA levels and was highly mutagenic. The high-temperature meat diet increased the mutagenicity of hydrolyzed urine and feces compared to the low-temperature meat diet. The mutagenicity of hydrolyzed urine was increased nearly twofold by the inhibitor diet, indicating that the inhibitors enhanced conjugation. Inhibitors decreased significantly the mutagenicity of un-hydrolyzed and hydrolyzed feces. The diets did not alter the levels of DNA damage in non-target white blood cells, but the inhibitor diet decreased nearly twofold the DNA damage in target colorectal cells. To our knowledge, this is the first demonstration that dietary factors can reduce DNA damage in the target tissue of fried-meat associated carcinogenesis.ClinicalTrials.gov NCT00340743

Metabolism of 2-Chloro-4-Nitrophenol in a Gram Negative Bacterium, Burkholderia sp. RKJ 800

A 2-Chloro-4-nitrophenol (2C4NP) degrading bacterial strain designated as RKJ 800 was isolated from a pesticide contaminated site of India by enrichment method and utilized 2C4NP as sole source of carbon and energy. The stoichiometric amounts of nitrite and chloride ions were detected during the degradation of 2C4NP. On the basis of thin layer chromatography, high performance liquid chromatography and gas chromatography-mass spectrometry, chlorohydroquinone (CHQ) and hydroquinone (HQ) were identified as major metabolites of the degradation pathway of 2C4NP. Manganese dependent HQ dioxygenase activity was observed in the crude extract of 2C4NP induced cells of the strain RKJ 800 that suggested the cleavage of the HQ to γ-hydroxymuconic semialdehyde. On the basis of the 16S rRNA gene sequencing, strain RKJ 800 was identified as a member of genus Burkholderia. Our studies clearly showed that Burkholderia sp. RKJ 800 degraded 2-chloro-4-nitrophenol via hydroquinone pathway. The pathway identified in a gram negative bacterium, Burkholderia sp. strain RKJ 800 was differed from previously reported 2C4NP degradation pathway in another gram-negative Burkholderia sp. SJ98. This is the first report of the formation of CHQ and HQ in the degradation of 2C4NP by any gram-negative bacteria. Laboratory-scale soil microcosm studies showed that strain RKJ 800 is a suitable candidate for bioremediation of 2C4NP contaminated sites

Discovery of DNA methylation markers in cervical cancer using relaxation ranking

<p>Abstract</p> <p>Background</p> <p>To discover cancer specific DNA methylation markers, large-scale screening methods are widely used. The pharmacological unmasking expression microarray approach is an elegant method to enrich for genes that are silenced and re-expressed during functional reversal of DNA methylation upon treatment with demethylation agents. However, such experiments are performed in <it>in vitro </it>(cancer) cell lines, mostly with poor relevance when extrapolating to primary cancers. To overcome this problem, we incorporated data from primary cancer samples in the experimental design. A strategy to combine and rank data from these different data sources is essential to minimize the experimental work in the validation steps.</p> <p>Aim</p> <p>To apply a new relaxation ranking algorithm to enrich DNA methylation markers in cervical cancer.</p> <p>Results</p> <p>The application of a new sorting methodology allowed us to sort high-throughput microarray data from both cervical cancer cell lines and primary cervical cancer samples. The performance of the sorting was analyzed <it>in silico</it>. Pathway and gene ontology analysis was performed on the top-selection and gives a strong indication that the ranking methodology is able to enrich towards genes that might be methylated. Terms like regulation of progression through cell cycle, positive regulation of programmed cell death as well as organ development and embryonic development are overrepresented. Combined with the highly enriched number of imprinted and X-chromosome located genes, and increased prevalence of known methylation markers selected from cervical (the highest-ranking known gene is <it>CCNA1</it>) as well as from other cancer types, the use of the ranking algorithm seems to be powerful in enriching towards methylated genes.</p> <p>Verification of the DNA methylation state of the 10 highest-ranking genes revealed that 7/9 (78%) gene promoters showed DNA methylation in cervical carcinomas. Of these 7 genes, 3 (<it>SST</it>, <it>HTRA3 </it>and <it>NPTX1</it>) are not methylated in normal cervix tissue.</p> <p>Conclusion</p> <p>The application of this new relaxation ranking methodology allowed us to significantly enrich towards methylation genes in cancer. This enrichment is both shown <it>in silico </it>and by experimental validation, and revealed novel methylation markers as proof-of-concept that might be useful in early cancer detection in cervical scrapings.</p

ALMA 26 arcmin² Survey of GOODS-S at One-millimeter (ASAGAO):X-Ray AGN Properties of Millimeter-selected Galaxies

We investigate the X-ray active galactic nucleus (AGN) properties of millimeter galaxies in the Great Observatories Origins Deep Survey South (GOODS-S) field detected with the Atacama Large Millimeter/submillimeter Array (ALMA), by utilizing the Chandra 7-Ms data, the deepest X-ray survey to date. Our millimeter galaxy sample comes from the ASAGAO survey covering 26 arcmin$^2$ (12 sources at a 1.2-mm flux-density limit of $\approx$0.6 mJy), supplemented by the deeper but narrower 1.3-mm survey of a part of the ASAGAO field by Dunlop et al.\ (2017). Fourteen out of the total 25 millimeter galaxies have Chandra counterparts. The observed AGN fractions at $z=1.5-3$ is found to be 90$^{+8}_{-19}$\% and $57^{+23}_{-25}$\% for the ultra/luminous infrared galaxies with $\log L_{\rm IR}/L_{\odot} = 12-12.8$ and $\log L_{\rm IR}/L_{\odot} = 11.5-12$, respectively. The majority ($\sim$2/3) of the ALMA and/or Herschel detected X-ray AGNs at $z=1.5-3$ appear to be star-formation dominant populations, having $L_{\rm X}$/ $L_{\rm IR}$ ratios smaller than the "simultaneous evolution" value expected from the local black-hole mass to stellar mass ($M_{\rm BH}$-$M_*$) relation. On the basis of the $L_{\rm X}$ and stellar mass relation, we infer that a large fraction of star-forming galaxies at $z=1.5-3$ have black hole masses smaller than those expected from the local $M_{\rm BH}$-$M_*$ relation. This is opposite to previous reports on luminous AGN at same redshifts detected in wider and shallower surveys, which are subject to selection biases against lower luminosity AGN. Our results are consistent with an evolutionary scenario that star formation occurs first, and an AGN-dominant phase follows later, in objects finally evolving into galaxies with classical bulges.Comment: 14 pages including 5 figures and 1 table, accepted for publication in Ap

Lineage-specific distribution of high levels of genomic 5-hydroxymethylcytosine in mammalian development

Methylation of cytosine is a DNA modification associated with gene repression. Recently, a novel cytosine modification, 5-hydroxymethylcytosine (5-hmC) has been discovered. Here we examine 5-hmC distribution during mammalian development and in cellular systems, and show that the developmental dynamics of 5-hmC are different from those of 5-methylcytosine (5-mC); in particular 5-hmC is enriched in embryonic contexts compared to adult tissues. A detectable 5-hmC signal appears in pre-implantation development starting at the zygote stage, where the paternal genome is subjected to a genome-wide hydroxylation of 5-mC, which precisely coincides with the loss of the 5-mC signal in the paternal pronucleus. Levels of 5-hmC are high in cells of the inner cell mass in blastocysts, and the modification colocalises with nestin-expressing cell populations in mouse post-implantation embryos. Compared to other adult mammalian organs, 5-hmC is strongly enriched in bone marrow and brain, wherein high 5-hmC content is a feature of both neuronal progenitors and post-mitotic neurons. We show that high levels of 5-hmC are not only present in mouse and human embryonic stem cells (ESCs) and lost during differentiation, as has been reported previously, but also reappear during the generation of induced pluripotent stem cells; thus 5-hmC enrichment correlates with a pluripotent cell state. Our findings suggest that apart from the cells of neuronal lineages, high levels of genomic 5-hmC are an epigenetic feature of embryonic cell populations and cellular pluri- and multi-lineage potency. To our knowledge, 5-hmC represents the first epigenetic modification of DNA discovered whose enrichment is so cell-type specific

In Vivo Control of CpG and Non-CpG DNA Methylation by DNA Methyltransferases

The enzymatic control of the setting and maintenance of symmetric and non-symmetric DNA methylation patterns in a particular genome context is not well understood. Here, we describe a comprehensive analysis of DNA methylation patterns generated by high resolution sequencing of hairpin-bisulfite amplicons of selected single copy genes and repetitive elements (LINE1, B1, IAP-LTR-retrotransposons, and major satellites). The analysis unambiguously identifies a substantial amount of regional incomplete methylation maintenance, i.e. hemimethylated CpG positions, with variant degrees among cell types. Moreover, non-CpG cytosine methylation is confined to ESCs and exclusively catalysed by Dnmt3a and Dnmt3b. This sequence position–, cell type–, and region-dependent non-CpG methylation is strongly linked to neighboring CpG methylation and requires the presence of Dnmt3L. The generation of a comprehensive data set of 146,000 CpG dyads was used to apply and develop parameter estimated hidden Markov models (HMM) to calculate the relative contribution of DNA methyltransferases (Dnmts) for de novo and maintenance DNA methylation. The comparative modelling included wild-type ESCs and mutant ESCs deficient for Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3a/3b, respectively. The HMM analysis identifies a considerable de novo methylation activity for Dnmt1 at certain repetitive elements and single copy sequences. Dnmt3a and Dnmt3b contribute de novo function. However, both enzymes are also essential to maintain symmetrical CpG methylation at distinct repetitive and single copy sequences in ESCs