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

Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer

Background:Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer. In this study, we investigated the prognostic impact of PODXL expression in colorectal cancer (CRC).Methods:Using tissue microarrays and immunohistochemistry, PODXL expression was evaluated in 536 incident CRC cases from a prospective, population-based cohort study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the impact of PODXL expression on cancer-specific survival (CSS) and overall survival (OS).Results:High PODXL expression was significantly associated with unfavourable clinicopathological characteristics, a shorter CSS (hazard ratio (HR)=1.98; 95% confidence interval (CI) 1.38-2.84, P<0.001) and 5-year OS (HR=1.85; 95% CI 1.29-2.64, P=0.001); the latter remaining significant in multivariate analysis (HR=1.52; 95% CI 1.03-2.25, P=0.036). In addition, in curatively resected stage III (T1-4, N1-2, M0) patients (n=122) with tumours with high PODXL expression, a significant benefit from adjuvant chemotherapy was demonstrated (p(interaction) =0.004 for CSS and 0.015 for 5-year OS in multivariate analysis).Conclusion:Podocalyxin-like 1 expression is an independent factor of poor prognosis in CRC. Our results also suggest that PODXL may be a useful marker to stratify patients for adjuvant chemotherapy

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

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

The E. coli Anti-Sigma Factor Rsd: Studies on the Specificity and Regulation of Its Expression

Background: Among the seven different sigma factors in E. coli s 70 has the highest concentration and affinity for the core RNA polymerase. The E. coli protein Rsd is regarded as an anti-sigma factor, inhibiting s 70-dependent transcription at the onset of stationary growth. Although binding of Rsd to s 70 has been shown and numerous structural studies on Rsd have been performed the detailed mechanism of action is still unknown. Methodology/Principal Findings: We have performed studies to unravel the function and regulation of Rsd expression in vitro and in vivo. Cross-linking and affinity binding revealed that Rsd is able to interact with s 70, with the core enzyme of RNA polymerase and is able to form dimers in solution. Unexpectedly, we find that Rsd does also interact with s 38, the stationary phase-specific sigma factor. This interaction was further corroborated by gel retardation and footprinting studies with different promoter fragments and s 38-ors 70-containing RNA polymerase in presence of Rsd. Under competitive in vitro transcription conditions, in presence of both sigma factors, a selective inhibition of s 70-dependent transcription was prevailing, however. Analysis of rsd expression revealed that the nucleoid-associated proteins H-NS and FIS, StpA and LRP bind to the regulatory region of the rsd promoters. Furthermore, the major promoter P2 was shown to be down-regulated in vivo by RpoS, the stationary phase-specific sigma factor and the transcription factor DksA, while induction of the stringent control enhanced rsd promoter activity. Most notably, the dam-dependent methylation of a cluster of GATC sites turned ou

Bacterial Leaf Symbiosis in Angiosperms: Host Specificity without Co-Speciation

Bacterial leaf symbiosis is a unique and intimate interaction between bacteria and flowering plants, in which endosymbionts are organized in specialized leaf structures. Previously, bacterial leaf symbiosis has been described as a cyclic and obligate interaction in which the endosymbionts are vertically transmitted between plant generations and lack autonomous growth. Theoretically this allows for co-speciation between leaf nodulated plants and their endosymbionts. We sequenced the nodulated Burkholderia endosymbionts of 54 plant species from known leaf nodulated angiosperm genera, i.e. Ardisia, Pavetta, Psychotria and Sericanthe. Phylogenetic reconstruction of bacterial leaf symbionts and closely related free-living bacteria indicates the occurrence of multiple horizontal transfers of bacteria from the environment to leaf nodulated plant species. This rejects the hypothesis of a long co-speciation process between the bacterial endosymbionts and their host plants. Our results indicate a recent evolutionary process towards a stable and host specific interaction confirming the proposed maternal transmission mode of the endosymbionts through the seeds. Divergence estimates provide evidence for a relatively recent origin of bacterial leaf symbiosis, dating back to the Miocene (5–23 Mya). This geological epoch was characterized by cool and arid conditions, which may have triggered the origin of bacterial leaf symbiosis

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

Keratan sulphate in the tumour environment

Keratan sulphate (KS) is a bioactive glycosaminoglycan (GAG) of some complexity composed of the repeat disaccharide D-galactose β1→4 glycosidically linked to N-acetyl glucosamine. During the biosynthesis of KS, a family of glycosyltransferase and sulphotransferase enzymes act sequentially and in a coordinated fashion to add D-galactose (D-Gal) then N-acetyl glucosamine (GlcNAc) to a GlcNAc acceptor residue at the reducing terminus of a nascent KS chain to effect chain elongation. D-Gal and GlcNAc can both undergo sulphation at C6 but this occurs more frequently on GlcNAc than D-Gal. Sulphation along the developing KS chain is not uniform and contains regions of variable length where no sulphation occurs, regions which are monosulphated mainly on GlcNAc and further regions of high sulphation where both of the repeat disaccharides are sulphated. Each of these respective regions in the KS chain can be of variable length leading to KS complexity in terms of chain length and charge localization along the KS chain. Like other GAGs, it is these variably sulphated regions in KS which define its interactive properties with ligands such as growth factors, morphogens and cytokines and which determine the functional properties of tissues containing KS. Further adding to KS complexity is the identification of three different linkage structures in KS to asparagine (N-linked) or to threonine or serine residues (O-linked) in proteoglycan core proteins which has allowed the categorization of KS into three types, namely KS-I (corneal KS, N-linked), KS-II (skeletal KS, O-linked) or KS-III (brain KS, O-linked). KS-I to -III are also subject to variable addition of L-fucose and sialic acid groups. Furthermore, the GlcNAc residues of some members of the mucin-like glycoprotein family can also act as acceptor molecules for the addition of D-Gal and GlcNAc residues which can also be sulphated leading to small low sulphation glycoforms of KS. These differ from the more heavily sulphated KS chains found on proteoglycans. Like other GAGs, KS has evolved molecular recognition and information transfer properties over hundreds of millions of years of vertebrate and invertebrate evolution which equips them with cell mediatory properties in normal cellular processes and in aberrant pathological situations such as in tumourogenesis. Two KS-proteoglycans in particular, podocalyxin and lumican, are cell membrane, intracellular or stromal tissue–associated components with roles in the promotion or regulation of tumour development, mucin-like KS glycoproteins may also contribute to tumourogenesis. A greater understanding of the biology of KS may allow better methodology to be developed to more effectively combat tumourogenic processes