Microbes with higher metabolic independence are enriched in human gut microbiomes under stress

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health versus IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments

Structural properties of discs and bulges of early-type galaxies

We have used the EFAR sample of galaxies to study the light distributions of early-type galaxies. We decompose the 2D light distribution of the galaxies in a flattened spheroidal component with a Sersic radial light profile and an inclined disc component with an exponential light profile. We show that the brightest, bulge dominated elliptical galaxies have a fairly broad distribution in the Sersic profile shape parameter n_B, with a median of about 3.7 and a sigma of ~0.9. Other galaxies have smaller n_B values, meaning that spheroids are in general less concentrated than the n_B=4 de Vaucouleurs-law profile. The results of our light decompositions are robust, even though without kinematic information we cannot prove that the spheroids and discs are really pressure- and rotation-supported stellar systems. If we assume that the detected spheroids and discs are indeed separate components, we can draw the following conclusions: 1) the spheroid and disc scale sizes are correlated; 2) bulge-to-total luminosity ratios, bulge effective radii, and bulge n_B values are all positively correlated; 3) the bivariate space density distribution of elliptical galaxies in the (luminosity, scale size)-plane is well described by a Schechter luminosity function in and a log-normal scale-size distribution at a given luminosity; 4) at the brightest luminosities, the scale size distribution of elliptical galaxies is similar to those of bright spiral galaxies; at fainter luminosities the elliptical scale size distribution peaks at distinctly smaller sizes than the spiral galaxy distribution; and 5) bulge components of early-type galaxies are typically a factor 1.5 to 2.5 smaller than the disks of spiral galaxies, while disc components of early-type galaxies are typically twice as large as the discs of spiral galaxies. [abridged]Comment: 16 pages, 18 figures. Accepted for publication in the MNRA

Unifying the known and unknown microbial coding sequence space

5 figures, 13 appendixes.-- Data availability: We used public data as described in the Methods section and Appendix 1-table 5.The code used for the analyses in the manuscript is available at https://github.com/functional-dark-side/functional-dark-side.github.io/tree/master/scripts. A list with the program versions can be found in https://github.com/functional-dark-side/functional-dark-side.github.io/blob/master/programs_and_versions.txt.The code to create the figures is available at https://github.com/functional-dark-side/vanni_et_al-figures, and the data for the figure can be downloaded from https://doi.org/10.6084/m9.figshare.12738476.v2. A reproducible version of the workflow is available at https://github.com/functional-dark-side/agnostos-wf.The data is publicly available at https://doi.org/10.6084/m9.figshare.12459056Genes of unknown function are among the biggest challenges in molecular biology, especially in microbial systems, where 40%-60% of the predicted genes are unknown. Despite previous attempts, systematic approaches to include the unknown fraction into analytical workflows are still lacking. Here, we present a conceptual framework, its translation into the computational workflow AGNOSTOS and a demonstration on how we can bridge the known-unknown gap in genomes and metagenomes. By analyzing 415,971,742 genes predicted from 1,749 metagenomes and 28,941 bacterial and archaeal genomes, we quantify the extent of the unknown fraction, its diversity, and its relevance across multiple organisms and environments. The unknown sequence space is exceptionally diverse, phylogenetically more conserved than the known fraction and predominantly taxonomically restricted at the species level. From the 71M genes identified to be of unknown function, we compiled a collection of 283,874 lineage-specific genes of unknown function for Cand. Patescibacteria (also known as Candidate Phyla Radiation, CPR), which provides a significant resource to expand our understanding of their unusual biology. Finally, by identifying a target gene of unknown function for antibiotic resistance, we demonstrate how we can enable the generation of hypotheses that can be used to augment experimental data.The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by Barcelona Supercomputing Center (RES-AECT-2014-2-0085), the BMBF877 funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) (031A537B, 031A533A, 031A538A, 031A533B, 031A535A, 031A537C, 031A534A, 031A532B), the University of Oxford Advanced Research Computing (http://dx.doi.org/10.5281/zenodo.22558) and the MARBITS bioinformatics core at ICM-CSIC.CV was supported by the Max Planck Society. AFG received funding from the European Union’s Horizon 2020 research and innovation program Blue Growth: Unlocking the potential of Seas and Oceans under grant agreement no. 634486 (project acronym INMARE). AM was supported by the Biotechnology and Biological Sciences Research Council [BB/M011755/1, BB/R015228/1] and RDF by the European Molecular Biology Laboratory core funds. EOC was supported by project INTERACTOMA RTI2018-101205-B-I00 from the Spanish Agency of Science MICIU/AEI. S 887 GA and PS received additional funding by the project MAGGY (CTM2017-87736-R) from the Spanish Ministry of Economy and Competitiveness. The Malaspina 2010 Expedition was supported by the Spanish Ministry of Economy and Competitiveness (MINECO) through the Consolider-Ingenio program (ref. CSD2008-00077). The authors thank Johannes Söding and Alex Bateman for helpful discussions.Peer reviewedWith the institutional support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)

The James Webb Space Telescope

The James Webb Space Telescope (JWST) is a large (6.6m), cold (50K), infrared-optimized space observatory that will be launched early in the next decade. The observatory will have four instruments: a near-infrared camera, a near-infrared multi-object spectrograph, and a tunable filter imager will cover the wavelength range, 0.6 to 5.0 microns, while the mid-infrared instrument will do both imaging and spectroscopy from 5.0 to 29 microns. The JWST science goals are divided into four themes. The End of the Dark Ages: First Light and Reionization theme seeks to identify the first luminous sources to form and to determine the ionization history of the early universe. The Assembly of Galaxies theme seeks to determine how galaxies and the dark matter, gas, stars, metals, morphological structures, and active nuclei within them evolved from the epoch of reionization to the present day. The Birth of Stars and Protoplanetary Systems theme seeks to unravel the birth and early evolution of stars, from infall on to dust-enshrouded protostars to the genesis of planetary systems. The Planetary Systems and the Origins of Life theme seeks to determine the physical and chemical properties of planetary systems including our own, and investigate the potential for the origins of life in those systems. To enable these observations, JWST consists of a telescope, an instrument package, a spacecraft and a sunshield. The telescope consists of 18 beryllium segments, some of which are deployed. The segments will be brought into optical alignment on-orbit through a process of periodic wavefront sensing and control. The JWST operations plan is based on that used for previous space observatories, and the majority of JWST observing time will be allocated to the international astronomical community through annual peer-reviewed proposal opportunities.Comment: 96 pages, including 48 figures and 15 tables, accepted by Space Science Review

Observations of Lyα\alpha Emitters at High Redshift

In this series of lectures, I review our observational understanding of high-$z$ Ly$\alpha$ emitters (LAEs) and relevant scientific topics. Since the discovery of LAEs in the late 1990s, more than ten (one) thousand(s) of LAEs have been identified photometrically (spectroscopically) at $z\sim 0$ to $z\sim 10$. These large samples of LAEs are useful to address two major astrophysical issues, galaxy formation and cosmic reionization. Statistical studies have revealed the general picture of LAEs' physical properties: young stellar populations, remarkable luminosity function evolutions, compact morphologies, highly ionized inter-stellar media (ISM) with low metal/dust contents, low masses of dark-matter halos. Typical LAEs represent low-mass high-$z$ galaxies, high-$z$ analogs of dwarf galaxies, some of which are thought to be candidates of population III galaxies. These observational studies have also pinpointed rare bright Ly$\alpha$ sources extended over $\sim 10-100$ kpc, dubbed Ly$\alpha$ blobs, whose physical origins are under debate. LAEs are used as probes of cosmic reionization history through the Ly$\alpha$ damping wing absorption given by the neutral hydrogen of the inter-galactic medium (IGM), which complement the cosmic microwave background radiation and 21cm observations. The low-mass and highly-ionized population of LAEs can be major sources of cosmic reionization. The budget of ionizing photons for cosmic reionization has been constrained, although there remain large observational uncertainties in the parameters. Beyond galaxy formation and cosmic reionization, several new usages of LAEs for science frontiers have been suggested such as the distribution of {\sc Hi} gas in the circum-galactic medium and filaments of large-scale structures. On-going programs and future telescope projects, such as JWST, ELTs, and SKA, will push the horizons of the science frontiers.Comment: Lecture notes for `Lyman-alpha as an Astrophysical and Cosmological Tool', Saas-Fee Advanced Course 46. Verhamme, A., North, P., Cantalupo, S., & Atek, H. (eds.) --- 147 pages, 103 figures. Abstract abridged. Link to the lecture program including the video recording and ppt files : https://obswww.unige.ch/Courses/saas-fee-2016/program.cg

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Outcomes in Kidney Transplant Recipients From Older Living Donors

Background. Previous studies demonstrate that graft survival from older living kidney donors (LD; age >60 years) is worse than younger LD but similar to deceased standard criteria donors (SCD). Limited sample size has precluded more detailed analyses of transplants from older LD. Methods. Using the United Network for Organ Sharing database from 1994 to 2012, recipients were categorized by donor status: SCD, expanded criteria donor (ECD), or LD (by donor age: = 70 years). Adjustedmodels, controlling for donor and recipient risk factors, evaluated graft and recipient survivals. Results. Of 250,827 kidney transplants during the study period, 92,646 were LD kidneys, with 4.5% of these recipients (n = 4,186) transplanted with older LD kidneys. The use of LD donors 60 years or older increased significantly from 3.6% in 1994 to 7.4% in 2011. Transplant recipients with older LD kidneys had significantly lower graft and overall survival compared to younger LD recipients. Compared to SCD recipients, graft survival was decreased in recipients with LD 70 years or older, but overall survival was similar. Older LD kidney recipients had better graft and overall survival than ECD recipients. Conclusions. As use of older kidney donors increases, overall survival among kidney transplant recipients from older living donors was similar to or better than SCD recipients, better than ECD recipients, but worse than younger LD recipients. With increasing kidney donation from older adults to alleviate profound organ shortages, the use of older kidney donors appears to be an equivalent or beneficial alternative to awaiting deceased donor kidneys

Surgical Versus Percutaneous Closure of PDA in Preterm Infants: Procedural Charges and Outcomes

Studies comparing percutaneous closure of patent ductus arteriosus (PDA) with surgical ligation tend to exclude premature infants and have not assessed procedural charges. We compared our contemporary outcomes and charges of device closure to surgical ligation of PDA in preterm infants. Preterm infants who underwent isolated PDA closure during their newborn hospitalization (January 2014 to September 2017) were grouped based on intention to treat (surgery versus device closure). Patient demographics, procedural details, and immediate postprocedural outcomes were compared. Procedural charges for device closure versus surgical ligation were compared. Compared with the device group (n = 33), patients undergoing surgical ligation (n = 39) were younger, smaller, and required more preoperative support (P < 0.05). The procedure time was shorter for surgical ligation (P < 0.01). Although there was no procedural mortality in either group, the complication rate was higher for device closure than for surgical ligation (15.2% versus 0%; P = 0.02). The proportion of patients returning to preprocedural respiratory support by 48 h after procedure was similar. There was a higher proportion of surgical patients who required increased inotropic support in the first 24 h after procedure (P = 0.19). The procedural charges for transcatheter device closure were twice as expensive as those for surgical ligation. In our early experience with percutaneous PDA closure, we found a percutaneous approach in preterm infants feasible and well tolerated. Both surgical ligation and device closure were associated with perioperative or postoperative complications. Procedural charges were higher for percutaneous closure, driven by device charge and catheterization room utilization. Further investigation is needed to establish guidelines for first-line therapy for PDA closure in preterm infants, including cost-benefit analysis