Photodissociation and the Morphology of HI in Galaxies

Young massive stars produce Far-UV photons which dissociate the molecular gas on the surfaces of their parent molecular clouds. Of the many dissociation products which result from this ``back-reaction'', atomic hydrogen \HI is one of the easiest to observe through its radio 21-cm hyperfine line emission. In this paper I first review the physics of this process and describe a simplified model which has been developed to permit an approximate computation of the column density of photodissociated \HI which appears on the surfaces of molecular clouds. I then review several features of the \HI morphology of galaxies on a variety of length scales and describe how photodissociation might account for some of these observations. Finally, I discuss several consequences which follow if this view of the origin of HI in galaxies continues to be successful.Comment: 18 pages, 7 figures in 8 files, invited review paper for the conference "Penetrating Bars Through Masks of Cosmic Dust: The Hubble Tuning Fork Strikes a New Note", South Africa, June 2004. Proceedings to be published by Kluwer, eds. D.L. Block, K.C. Freeman, I. Puerari, R. Groess, & E.K. Bloc

Interaction-dependent photon-assisted tunneling in optical lattices: a quantum simulator of strongly-correlated electrons and dynamical gauge fields

We introduce a scheme that combines photon-assisted tunneling by a moving optical lattice with strong Hubbard interactions, and allows for the quantum simulation of paradigmatic quantum many-body models. We show that, in a certain regime, this quantum simulator yields an effective Hubbard Hamiltonian with tunable bond-charge interactions, a model studied in the context of strongly-correlated electrons. In a different regime, we show how to exploit a correlated destruction of tunneling to explore Nagaoka ferromagnetism at finite Hubbard repulsion. By changing the photon-assisted tunneling parameters, we can also obtain a t-J model with independently controllable tunneling t, super-exchange interaction J, and even a Heisenberg-Ising anisotropy. Hence, the full phase diagram of this paradigmatic model becomes accessible to cold-atom experiments, departing from the region t _ J allowed by standard single-band Hubbard Hamiltonians in the strong-repulsion limit. We finally show that, by generalizing the photon-assisted tunneling scheme, the quantum simulator yields models of dynamical Gauge fields, where atoms of a given electronic state dress the tunneling of the atoms with a different internal state, leading to Peierls phases that mimic a dynamical magnetic field

Salmonella-Induced Mucosal Lectin RegIIIβ Kills Competing Gut Microbiota

Intestinal inflammation induces alterations of the gut microbiota and promotes overgrowth of the enteric pathogen Salmonella enterica by largely unknown mechanisms. Here, we identified a host factor involved in this process. Specifically, the C-type lectin RegIIIβ is strongly upregulated during mucosal infection and released into the gut lumen. In vitro, RegIIIβ kills diverse commensal gut bacteria but not Salmonella enterica subspecies I serovar Typhimurium (S. Typhimurium). Protection of the pathogen was attributable to its specific cell envelope structure. Co-infection experiments with an avirulent S. Typhimurium mutant and a RegIIIβ-sensitive commensal E. coli strain demonstrated that feeding of RegIIIβ was sufficient for suppressing commensals in the absence of all other changes inflicted by mucosal disease. These data suggest that RegIIIβ production by the host can promote S. Typhimurium infection by eliminating inhibitory gut microbiota

Coherent dynamics of Bose-Einstein condensates in high-finesse optical cavities

We study the mutual interaction of a Bose-Einstein condensed gas with a single mode of a high-finesse optical cavity. We show how the cavity transmission reflects condensate properties and calculate the self-consistent intra-cavity light field and condensate evolution. Solving the coupled condensate-cavity equations we find that while falling through the cavity, the condensate is adiabatically transfered into the ground state of the periodic optical potential. This allows time dependent non-destructive measurements on Bose-Einstein condensates with intriguing prospects for subsequent controlled manipulation.Comment: 5 pages, 5 figures; revised version: added reference

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

The XMM-Newton serendipitous ultraviolet source survey catalogue

The XMM-Newton Serendipitous Ultraviolet Source Survey (XMM-SUSS) is a catalogue of ultraviolet (UV) sources detected serendipitously by the Optical Monitor (XMM-OM) on-board the XMM-Newton observatory. The catalogue contains ultraviolet-detected sources collected from 2,417 XMM-OM observations in 1-6 broad band UV and optical filters, made between 24 February 2000 and 29 March 2007. The primary contents of the catalogue are source positions, magnitudes and fluxes in 1 to 6 passbands, and these are accompanied by profile diagnostics and variability statistics. The XMM-SUSS is populated by 753,578 UV source detections above a 3 sigma signal-to-noise threshold limit which relate to 624,049 unique objects. Taking account of substantial overlaps between observations, the net sky area covered is 29-54 square degrees, depending on UV filter. The magnitude distributions peak at 20.2, 20.9 and 21.2 in UVW2, UVM2 and UVW1 respectively. More than 10 per cent of sources have been visited more than once using the same filter during XMM-Newton operation, and > 20 per cent of sources are observed more than once per filter during an individual visit. Consequently, the scope for science based on temporal source variability on timescales of hours to years is broad. By comparison with other astrophysical catalogues we test the accuracy of the source measurements and define the nature of the serendipitous UV XMM-OM source sample. The distributions of source colours in the UV and optical filters are shown together with the expected loci of stars and galaxies, and indicate that sources which are detected in multiple UV bands are predominantly star-forming galaxies and stars of type G or earlier.Comment: Accepted for publication in MNRA

Pathway-Based High-Throughput Chemical Screen Identifies Compounds That Decouple Heterochromatin Transformations

Heterochromatin protein 1 (HP1) facilitates the formation of repressive heterochromatin domains by recruiting histone lysine methyltransferase enzymes to chromatin, resulting in increased levels of histone H3K9me3. To identify chemical inhibitors of the HP1-heterochromatin gene repression pathway, we combined a cell-based assay that utilized chemical-mediated recruitment of HP1 to an endogenous active gene with high-throughput flow cytometry. Here we characterized small molecule inhibitors that block HP1-mediated heterochromatin formation. Our lead compounds demonstrated dose-dependent inhibition of HP1-stimulated gene repression and were validated in an orthogonal cell-based system. One lead inhibitor was improved by a change in stereochemistry, resulting in compound 2, which was further used to decouple the inverse relationship between H3K9 and H3K4 methylation states. We identified molecular components that bound compound 2, either directly or indirectly, by chemical affinity purification with a biotin-tagged derivative, followed by quantitative proteomic techniques. In summary, our pathway-based chemical screening approach resulted in the discovery of new inhibitors of HP1-mediated heterochromatin formation while identifying exciting new molecular interactions in the pathway to explore in the future. This modular platform can be expanded to test a wide range of chromatin modification pathways yielding inhibitors that are cell permeable and function in a physiologically relevant setting

HIV-1 drug resistance in people on dolutegravir-based antiretroviral therapy:a collaborative cohort analysis

BACKGROUND The widespread use of the integrase strand transfer inhibitor (INSTI) dolutegravir in first-line and second-line antiretroviral therapy (ART) might facilitate emerging resistance. The DTG RESIST study combined data from HIV cohorts to examine patterns of drug resistance mutations (DRMs) and identify risk factors for dolutegravir resistance. METHODS We included cohorts with INSTI resistance data from two collaborations (ART Cohort Collaboration, International epidemiology Databases to Evaluate AIDS in Southern Africa), and the UK Collaborative HIV Cohort. Eight cohorts from Canada, France, Germany, Italy, the Netherlands, Switzerland, South Africa, and the UK contributed data on individuals who were viraemic on dolutegravir-based ART and underwent genotypic resistance testing. Individuals with unknown dolutegravir initiation date were excluded. Resistance levels were categorised using the Stanford algorithm. We identified risk factors for resistance using mixed-effects ordinal logistic regression models. FINDINGS We included 599 people with genotypic resistance testing on dolutegravir-based ART between May 22, 2013, and Dec 20, 2021. Most had HIV-1 subtype B (n=351, 59%), a third had been exposed to first-generation INSTIs (n=193, 32%), 70 (12%) were on dolutegravir dual therapy, and 18 (3%) were on dolutegravir monotherapy. INSTI DRMs were detected in 86 (14%) individuals; 20 (3%) had more than one mutation. Most (n=563, 94%) were susceptible to dolutegravir, seven (1%) had potential low, six (1%) low, 17 (3%) intermediate, and six (1%) high-level dolutegravir resistance. The risk of dolutegravir resistance was higher on dolutegravir monotherapy (adjusted odds ratio [aOR] 34·1, 95% CI 9·93-117) and dolutegravir plus lamivudine dual therapy (aOR 9·21, 2·20-38·6) compared with combination ART, and in the presence of potential low or low (aOR 5·23, 1·32-20·7) or intermediate or high-level (aOR 13·4, 4·55-39·7) nucleoside reverse transcriptase inhibitor (NRTI) resistance. INTERPRETATION Among people with viraemia on dolutegravir-based ART, INSTI DRMs and dolutegravir resistance were rare. NRTI resistance substantially increased the risk of dolutegravir resistance, which is of concern, notably in resource-limited settings. Monitoring is important to prevent resistance at the individual and population level and ensure the long-term sustainability of ART. FUNDING US National Institutes of Health, Swiss National Science Foundation

Like Will to Like: Abundances of Closely Related Species Can Predict Susceptibility to Intestinal Colonization by Pathogenic and Commensal Bacteria

The intestinal ecosystem is formed by a complex, yet highly characteristic microbial community. The parameters defining whether this community permits invasion of a new bacterial species are unclear. In particular, inhibition of enteropathogen infection by the gut microbiota ( = colonization resistance) is poorly understood. To analyze the mechanisms of microbiota-mediated protection from Salmonella enterica induced enterocolitis, we used a mouse infection model and large scale high-throughput pyrosequencing. In contrast to conventional mice (CON), mice with a gut microbiota of low complexity (LCM) were highly susceptible to S. enterica induced colonization and enterocolitis. Colonization resistance was partially restored in LCM-animals by co-housing with conventional mice for 21 days (LCMcon21). 16S rRNA sequence analysis comparing LCM, LCMcon21 and CON gut microbiota revealed that gut microbiota complexity increased upon conventionalization and correlated with increased resistance to S. enterica infection. Comparative microbiota analysis of mice with varying degrees of colonization resistance allowed us to identify intestinal ecosystem characteristics associated with susceptibility to S. enterica infection. Moreover, this system enabled us to gain further insights into the general principles of gut ecosystem invasion by non-pathogenic, commensal bacteria. Mice harboring high commensal E. coli densities were more susceptible to S. enterica induced gut inflammation. Similarly, mice with high titers of Lactobacilli were more efficiently colonized by a commensal Lactobacillus reuteri RR strain after oral inoculation. Upon examination of 16S rRNA sequence data from 9 CON mice we found that closely related phylotypes generally display significantly correlated abundances (co-occurrence), more so than distantly related phylotypes. Thus, in essence, the presence of closely related species can increase the chance of invasion of newly incoming species into the gut ecosystem. We provide evidence that this principle might be of general validity for invasion of bacteria in preformed gut ecosystems. This might be of relevance for human enteropathogen infections as well as therapeutic use of probiotic commensal bacteria

Human Intestinal Cells Modulate Conjugational Transfer of Multidrug Resistance Plasmids between Clinical Escherichia coli Isolates.

Bacterial conjugation in the human gut microbiota is believed to play a major role in the dissemination of antibiotic resistance genes and virulence plasmids. However, the modulation of bacterial conjugation by the human host remains poorly understood and there is a need for controlled systems to study this process. We established an in vitro co-culture system to study the interaction between human intestinal cells and bacteria. We show that the conjugation efficiency of a plasmid encoding an extended spectrum beta-lactamase is reduced when clinical isolates of Escherichia coli are co-cultured with human intestinal cells. We show that filtered media from co-cultures contain a factor that reduces conjugation efficiency. Protease treatment of the filtered media eliminates this inhibition of conjugation. This data suggests that a peptide or protein based factor is secreted on the apical side of the intestinal cells exposed to bacteria leading to a two-fold reduction in conjugation efficiency. These results show that human gut epithelial cells can modulate bacterial conjugation and may have relevance to gene exchange in the gut