Listeria motility increases the efficiency of epithelial invasion during intestinal infection

Listeria monocytogenes (Lm) is a food-borne pathogen that causes severe bacterial gastroenteritis, with high rates of hospitalization and mortality. Lm is ubiquitous in soil, water and livestock, and can survive and proliferate at low temperatures. Following oral ingestion of contaminated food, Lm crosses the epithelium through intestinal goblet cells in a mechanism mediated by Lm InlA binding host E-cadherin. Importantly, human infections typically occur with Lm growing at or below room temperature, which is flagellated and motile. Even though many important human bacterial pathogens are flagellated, little is known regarding the effect of Lm motility on invasion and immune evasion. Here, we used complementary imaging and computer modeling approaches to test the hypothesis that bacterial motility helps Lm locate and engage target cells permissive for invasion. Imaging explanted mouse and human intestine, we showed that Lm grown at room temperature uses motility to scan the epithelial surface and preferentially attach to target cells. Furthermore, we integrated quantitative parameters from our imaging experiments to construct a versatile layered cellular Potts model (L-CPM) that simulates host-pathogen dynamics. Simulated data are consistent with the hypothesis that bacterial motility enhances invasion by allowing bacteria to search the epithelial surface for their preferred invasion targets. Indeed, our model consistently predicts that motile bacteria invade twice as efficiently over the first hour of infection. We also examined how bacterial motility affected interactions with host cellular immunity. In a mouse model of persistent infection, we found that neutrophils migrated to the apical surface of the epithelium 5 hours post infection and interacted with Lm. Yet in contrast to the view that neutrophils hunt for bacteria, we found that these interactions were driven by motility of Lm-which moved at least ~50x faster than neutrophils. Furthermore, our L-CPM predicts that motile bacteria maintain their invasion advantage even in the presence of host phagocytes, with the balance between invasion and phagocytosis governed almost entirely by bacterial motility. In conclusion, our simulations provide insight into host pathogen interaction dynamics at the intestinal epithelial barrier early during infection

Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species

Star formation in the filament of S254-S258 OB complex: a cluster in the process of making

International audienceInfrared Dark Clouds (IRDCs) are ideal laboratories to study the initial processes of high-mass star and star cluster formation. We investigated star formation activity of an unexplored filamentary dark cloud (size ∼ 5.7 pc × 1.9 pc), which itself is part of a large filament (∼ 20 pc) located in the S254-S258 OB complex at a distance of 2.5 kpc. Using Multi-band Imaging Photometer (MIPS) Spitzer 24 µm data, we uncover 49 sources with signal-to-noise ratio greater than 5. We identified 45 sources as candidate young stellar objects (YSOs) of Class I, Flat-spectrum, and Class II nature. Additional 17 candidate YSOs (9 Class I and 8 Class II) are also identified using JHK and Wide-field Infrared Survey Explorer (WISE) photometry. We find that the protostar to Class II sources ratio (∼ 2) and the protostar fraction (∼ 70 %) of the region are high. When the protostar fraction compared to other young clusters, it suggests that the star formation in the dark cloud was possibly started only 1 Myr ago. Combining the near-infrared photometry of the YSO candidates with the theoretical evolutionary models, we infer that most of the candidate YSOs formed in the dark cloud are low-mass (< 2 M) in nature. We examine the spatial distribution of the YSOs and find that majority of them are linearly aligned along the highest column density line (N(H 2)∼ 1 × 10 22 cm −2) of the dark cloud along its long axis at mean nearest neighbor separation of ∼ 0.2 pc. Using observed properties of the YSOs, physical conditions of the cloud and a simple cylindrical model, we explore the possible star formation process of this filamentary dark cloud and suggest that gravitational fragmentation within the filament should have played a dominant role in the formation of the YSOs. From the total mass of the YSOs, gaseous mass associated with the dark cloud, and surrounding environment, we infer that the region is presently forming stars at an efficiency ∼ 3% and a rate ∼ 30 M Myr −1 , and may emerge to a richer cluster

Analytical and biological variability in biomarker measurement in the Hispanic Community Health Study/Study of Latinos

Biomarker variability, which includes within-individual variability (CVI), between-individual variability (CVG) and methodological variability (CVP+A) is an important determinant of our ability to detect biomarker-disease associations. Estimates of CVI and CVG may be population specific and little data exists on biomarker variability in diverse Hispanic populations. Hence, we evaluated all 3 components of biomarker variability in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) using repeat blood collections (n=58) and duplicate blood measurements (n = 761 – 929 depending on the biomarker)

Sub-millimeter Observations of Giant Molecular Clouds in the Large Magellanic Cloud: Temperature and Density as Determined from J=3-2 and J=1-0 transitions of CO

We have carried out sub-mm 12CO(J=3-2) observations of 6 giant molecular clouds (GMCs) in the Large Magellanic Cloud (LMC) with the ASTE 10m sub-mm telescope at a spatial resolution of 5 pc and very high sensitivity. We have identified 32 molecular clumps in the GMCs and revealed significant details of the warm and dense molecular gas with n(H2) $\sim$ 10$^{3-5}$ cm$^{-3}$ and Tkin $\sim$ 60 K. These data are combined with 12CO(J=1-0) and 13CO(J=1-0) results and compared with LVG calculations. We found that the ratio of 12CO(J=3-2) to 12CO(J=1-0) emission is sensitive to and is well correlated with the local Halpha flux. We interpret that differences of clump propeties represent an evolutionary sequence of GMCs in terms of density increase leading to star formation.Type I and II GMCs (starless GMCs and GMCs with HII regions only, respectively) are at the young phase of star formation where density does not yet become high enough to show active star formation and Type III GMCs (GMCs with HII regions and young star clusters) represents the later phase where the average density is increased and the GMCs are forming massive stars. The high kinetic temperature correlated with \Halpha flux suggests that FUV heating is dominant in the molecular gas of the LMC.Comment: 74 pages, including 41 figures, accepted for publication in ApJ

Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species

Comprehensive quality assessment for aphasia rehabilitation after stroke: Protocol for a multicentre, mixed-methods study

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women\u27s Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families

Autophagy Induction Is a Tor- and Tp53-Independent Cell Survival Response in a Zebrafish Model of Disrupted Ribosome Biogenesis

Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (tti(s450)), which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In tti(s450), the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, allowing intestinal epithelial cells to evade cell death. Inhibiting autophagy in tti(s450) larvae markedly reduces their lifespan. Somewhat surprisingly, autophagy induction in tti(s450) larvae is independent of the state of the Tor pathway and proceeds unabated in Tp53-mutant larvae. These data demonstrate that autophagy is a survival mechanism invoked in response to ribosomal stress. This response may be of relevance to therapeutic strategies aimed at killing cancer cells by targeting ribosome biogenesis. In certain contexts, these treatments may promote autophagy and contribute to cancer cells evading cell death.This research was funded by the National Health and Medical Research Council of Australia through Project grant 433614 (JKH), Program grant 487922 (JKH), a Senior Research Fellowship (JKH), and a Howard Florey Centenary Fellowship (HV). Operational Infrastructure Support was provided by the Victorian Government, Australia. Additional support was from Australian Research Council grant DP0346823 (GJL); NIH grant DK060322 (DYRS); and CDMRP, Department of Defense, USA W81XWH-10-1-0854 (KCE)