Neutral Gas Properties and Lyα\alpha Escape in Extreme Green Pea Galaxies

Mechanisms regulating the escape of Ly$\alpha$ photons and ionizing radiation remain poorly understood. To study these processes we analyze VLA 21cm observations of one Green Pea (GP), J160810+352809 (hereafter J1608), and HST COS spectra of 17 GP galaxies at $z<0.2$. All are highly ionized: J1608 has the highest [O III] $\lambda5007$/[O II] $\lambda3727$ for star-forming galaxies in SDSS, and the 17 GPs have [O III]/[O II] $\geq6.6$. We set an upper limit on J1608's HI mass of $\log M_{HI}/M_\odot=8.4$, near or below average compared to similar mass dwarf galaxies. In the COS sample, eight GPs show Ly$\alpha$ absorption components, six of which also have Ly$\alpha$ emission. The HI column densities derived from Ly$\alpha$ absorption are high, $\log N_{HI}/$cm$^{-2}=19-21$, well above the LyC optically thick limit. Using low-ionization absorption lines, we measure covering fractions (f_{\mbox{cov}}) of $0.1-1$, and find that f_{\mbox{cov}} strongly anti-correlates with Ly$\alpha$ escape fraction. Low covering fractions may facilitate Ly$\alpha$ and LyC escape through dense neutral regions. GPs with f_{\mbox{cov}}\sim1 all have low neutral gas velocities, while GPs with lower f_{\mbox{cov}}=0.2-0.6 have a larger range of velocities. Conventional mechanical feedback may help establish low f_{\mbox{cov}} in some cases, whereas other processes may be important for GPs with low velocities. Finally, we compare f_{\mbox{cov}} with proposed indicators of LyC escape. Ionizing photon escape likely depends on a combination of neutral gas geometry and kinematics, complicating the use of emission-line diagnostics for identifying LyC emitters.Comment: 21 pages, 11 figures, accepted for publication in Ap

Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

AIM: To investigate the accuracy of fungal dysbiosis in mucosa and stool for predicting the diagnosis of Crohn’s disease (CD). METHODS: Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer’s protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve (AUC) was calculated. RESULTS: All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9 (range: 6.7-17.8) years for CD children and 13.9 (3.25-18.6) years for controls, and 10/15 (67%) of the CD and 13/20 (65%) of the control subjects were boys. CD locations at diagnosis were ileal (L1) in 4 and colonic (L3) in 11 children, while CD behavior was non-stricturing and non-penetrating (B1) in 12 and stricturing (B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools (AUC = 0.85 ± 0.057) than in mucosa (AUC = 0.71 ± 0.067) (P < 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION: We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD. Key Words: Fungiome, Mycobiome, Crohn’s disease, Inflammation, Saudi children Core tip: We found high accuracy of fungal dysbiosis in predicting diagnosis of Crohn’s disease (CD), a finding similar to bacterial dysbiosis. However, the higher area under the curve for the fungal dysbiosis classifier in stool (0.85 ± 0.057) than in mucosa (0.71 ± 0.067) (P < 0.001), contrasts with bacterial studies, suggesting higher accuracy of stool samples. Although the clinical application of this finding is limited at present by the high cost of fungal analysis, such information is important from a scientific viewpoint, to increase the understanding of the role of fungal flora in CD and to stimulate further studies.The authors extend their appreciations to the Deanship of Scientific Research at King Saud University in Riyadh, Kingdom of Saudi Arabia for funding this work through Research Group No [RGP-1436-007]. This work was also supported by a grant from the Simons Foundation [No. 409704] to Kirill Korolev) and by the startup fund from Boston University to Kirill Korolev. Simulations were carried out on Shared Computing Cluster at Boston University. Rajita Menon was partially supported by a Hariri Graduate Fellowship from Boston University. Harland Winter, MD received support from Martin Schlaff and the Diane and Dorothy Brooks Foundation. (RGP-1436-007 - King Saud University in Riyadh, Kingdom of Saudi Arabia; 409704 - Simons Foundation; Boston University; Hariri Graduate Fellowship from Boston University; Diane and Dorothy Brooks Foundation)Published versio

MEPicides: Potent antimalarial prodrugs targeting isoprenoid biosynthesis

AbstractThe emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.</jats:p

Neutral Gas Properties and Lyα Escape in Extreme Green Pea Galaxies

Mechanisms regulating the escape of Lyα photons and ionizing radiation remain poorly understood. To study these processes, we analyze Very Large Array 21 cm observations of one Green Pea (GP), J160810+352809 (hereafter J1608), and Hubble Space Telescope Cosmic Origins Spectrograph (COS) spectra of 17 GP galaxies at . All are highly ionized: J1608 has the highest [O iii] λ5007/[O ii] λ3727 for star-forming galaxies in Sloan Digital Sky Survey, and the 17 GPs have [O iii]/[O ii] ≥ 6.6. We set an upper limit on J1608\u27s H i mass of , near or below average compared to similar-mass dwarf galaxies. In the COS sample, eight GPs show Lyα absorption components, six of which also have Lyα emission. The H i column densities derived from Lyα absorption are high, cm−2 = 19–21, well above the LyC optically thick limit. Using low-ionization absorption lines, we measure covering fractions () of 0.1–1 and find that strongly anticorrelates with Lyα escape fraction. Low covering fractions may facilitate Lyα and LyC escape through dense neutral regions. GPs with all have low neutral gas velocities, while GPs with lower have a larger range of velocities. Conventional mechanical feedback may help establish low in some cases, whereas other processes may be important for GPs with low velocities. Finally, we compare with proposed indicators of LyC escape. Ionizing photon escape likely depends on a combination of neutral gas geometry and kinematics, complicating the use of emission-line diagnostics for identifying LyC emitters

Incorporation of zebularine from its 2′-deoxyribonucleoside triphosphate derivative and activity as a template-coding nucleobase

Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) was studied as both a 2 ′-deoxyribosyl 5 ′-triphosphate derivative and as a template incorporated into an oligonucleotide. Using a novel pyrosequencing assay, zebularine acted as cytosine analog and was incorporated into DNA with a template pairing profile most similar to cytosine, pairing with greatest efficiency opposite guanine in the template strand. Guanine was incorporated with greater affinity than adenine opposite a zebularine in the template strand. Computer modeling of base-pairing structures supported a better fit of zebularine opposite guanine than adenine. Zebularine acts as a cytosine analog, which supports its activity as an inhibitor of cytosine methyltransferase.A.S.Y. is the recipient of a STOP Cancer Career Development Award and the T.Franklin Williams Scholars-American Society of Oncology Career Development Award. This work was sponsored in part by a grant from the Wright Foundation.Peer reviewe

The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease.

Recent molecular studies have revealed a highly complex bacterial assembly in the canine intestinal tract. There is mounting evidence that microbes play an important role in the pathogenesis of acute and chronic enteropathies of dogs, including idiopathic inflammatory bowel disease (IBD). The aim of this study was to characterize the bacterial microbiota in dogs with various gastrointestinal disorders. Fecal samples from healthy dogs (n = 32), dogs with acute non-hemorrhagic diarrhea (NHD; n = 12), dogs with acute hemorrhagic diarrhea (AHD; n = 13), and dogs with active (n = 9) and therapeutically controlled idiopathic IBD (n = 10) were analyzed by 454-pyrosequencing of the 16S rRNA gene and qPCR assays. Dogs with acute diarrhea, especially those with AHD, had the most profound alterations in their microbiome, as significant separations were observed on PCoA plots of unweighted Unifrac distances. Dogs with AHD had significant decreases in Blautia, Ruminococcaceae including Faecalibacterium, and Turicibacter spp., and significant increases in genus Sutterella and Clostridium perfringens when compared to healthy dogs. No significant separation on PCoA plots was observed for the dogs with IBD. Faecalibacterium spp. and Fusobacteria were, however, decreased in the dogs with clinically active IBD, but increased during time periods of clinically insignificant IBD, as defined by a clinical IBD activity index (CIBDAI). Results of this study revealed a bacterial dysbiosis in fecal samples of dogs with various GI disorders. The observed changes in the microbiome differed between acute and chronic disease states. The bacterial groups that were commonly decreased during diarrhea are considered to be important short-chain fatty acid producers and may be important for canine intestinal health. Future studies should correlate these observed phylogenetic differences with functional changes in the intestinal microbiome of dogs with defined disease phenotypes

Evaluation of the bacterial diversity in the feces of cattle using 16S rDNA bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP)

<p>Abstract</p> <p>Background</p> <p>The microbiota of an animal's intestinal tract plays important roles in the animal's overall health, productivity and well-being. There is still a scarcity of information on the microbial diversity in the gut of livestock species such as cattle. The primary reason for this lack of data relates to the expense of methods needed to generate such data. Here we have utilized a bacterial tag-encoded FLX 16s rDNA amplicon pyrosequencing (bTEFAP) approach that is able to perform diversity analyses of gastrointestinal populations. bTEFAP is relatively inexpensive in terms of both time and labor due to the implementation of a novel tag priming method and an efficient bioinformatics pipeline. We have evaluated the microbiome from the feces of 20 commercial, lactating dairy cows.</p> <p>Results</p> <p>Ubiquitous bacteria detected from the cattle feces included <it>Clostridium</it>, <it>Bacteroides, Porpyhyromonas, Ruminococcus, Alistipes, Lachnospiraceae, Prevotella, Lachnospira, Enterococcus, Oscillospira, Cytophage, Anaerotruncus</it>, and <it>Acidaminococcus </it>spp. Foodborne pathogenic bacteria were detected in several of the cattle, a total of 4 cows were found to be positive for <it>Salmonella </it>spp (tentative <it>enterica</it>) and 6 cows were positive for <it>Campylobacter </it>spp. (tentative <it>lanienae</it>).</p> <p>Conclusion</p> <p>Using bTEFAP we have examined the microbiota in the feces of cattle. As these methods continue to mature we will better understand the ecology of the major populations of bacteria the lower intestinal tract. This in turn will allow for a better understanding of ways in which the intestinal microbiome contributes to animal health, productivity and wellbeing.</p

Prospecting environmental mycobacteria: combined molecular approaches reveal unprecedented diversity

Background: Environmental mycobacteria (EM) include species commonly found in various terrestrial and aquatic environments, encompassing animal and human pathogens in addition to saprophytes. Approximately 150 EM species can be separated into fast and slow growers based on sequence and copy number differences of their 16S rRNA genes. Cultivation methods are not appropriate for diversity studies; few studies have investigated EM diversity in soil despite their importance as potential reservoirs of pathogens and their hypothesized role in masking or blocking M. bovis BCG vaccine. Methods: We report here the development, optimization and validation of molecular assays targeting the 16S rRNA gene to assess diversity and prevalence of fast and slow growing EM in representative soils from semi tropical and temperate areas. New primer sets were designed also to target uniquely slow growing mycobacteria and used with PCR-DGGE, tag-encoded Titanium amplicon pyrosequencing and quantitative PCR. Results: PCR-DGGE and pyrosequencing provided a consensus of EM diversity; for example, a high abundance of pyrosequencing reads and DGGE bands corresponded to M. moriokaense, M. colombiense and M. riyadhense. As expected pyrosequencing provided more comprehensive information; additional prevalent species included M. chlorophenolicum, M. neglectum, M. gordonae, M. aemonae. Prevalence of the total Mycobacterium genus in the soil samples ranged from 2.3×107 to 2.7×108 gene targets g−1; slow growers prevalence from 2.9×105 to 1.2×107 cells g−1. Conclusions: This combined molecular approach enabled an unprecedented qualitative and quantitative assessment of EM across soil samples. Good concordance was found between methods and the bioinformatics analysis was validated by random resampling. Sequences from most pathogenic groups associated with slow growth were identified in extenso in all soils tested with a specific assay, allowing to unmask them from the Mycobacterium whole genus, in which, as minority members, they would have remained undetected

First validation of high-resolution satellite-derived methane emissions from an active gas leak in the UK

Atmospheric methane (CH4) is the second-most-important anthropogenic greenhouse gas and has a 20-year global warming potential 82 times greater than carbon dioxide (CO2). Anthropogenic sources account for g1/4g% of global CH4 emissions, of which 20g% come from oil and gas exploration, production and distribution. High-resolution satellite-based imaging spectrometers are becoming important tools for detecting and monitoring CH4 point source emissions, aiding mitigation. However, validation of these satellite measurements, such as those from the commercial GHGSat satellite constellation, has so far not been documented for active leaks. Here we present the monitoring and quantification, by GHGSat's satellites, of the CH4 emissions from an active gas leak from a downstream natural gas distribution pipeline near Cheltenham, UK, in the spring and summer of 2023 and provide the first validation of the satellite-derived emission estimates using surface-based mobile greenhouse gas surveys. We also use a Lagrangian transport model, the UK Met Office's Numerical Atmospheric-dispersion Modelling Environment (NAME), to estimate the flux from both satellite-and ground-based observation methods and assess the leak's contribution to observed concentrations at a local tall tower site (30gkm away). We find GHGSat's emission estimates to be in broad agreement with those made from the in situ measurements. During the study period (March-June 2023) GHGSat's emission estimates are 236-1357gkggCH4gh-1, whereas the mobile surface measurements are 634-846gkggCH4gh-1. The large variability is likely down to variations in flow through the pipe and engineering works across the 11-week period. Modelled flux estimates in NAME are 181-1243gkggCH4gh-1, which are lower than the satellite-and mobile-survey-derived fluxes but are within the uncertainty. After detecting the leak in March 2023, the local utility company was contacted, and the leak was fixed by mid-June 2023. Our results demonstrate that GHGSat's observations can produce flux estimates that broadly agree with surface-based mobile measurements. Validating the accuracy of the information provided by targeted, high-resolution satellite monitoring shows how it can play an important role in identifying emission sources, including unplanned fugitive releases that are inherently challenging to identify, track, and estimate their impact and duration. Rapid, widespread access to such data to inform local action to address fugitive emission sources across the oil and gas supply chain could play a significant role in reducing anthropogenic contributions to climate change.</p