Implications of antimicrobial combinations in complex wound biofilms containing fungi

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while mono-treatment approaches influenced biofilm composition it had no discernible effect on overall quantity. Only by combining bacterial and fungal specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition

Development and characterisation of a novel three-dimensional inter-kingdom wound biofilm model

Chronic diabetic foot ulcers are frequently colonised and infected by polymicrobial biofilms that ultimately prevent healing. This study aimed to create a novel in vitro inter-kingdom wound biofilm model on complex hydrogel-based cellulose substrata to test commonly used topical wound treatments. Inter-kingdom triadic biofilms composed of Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus were shown to be quantitatively greater in this model compared to a simple substratum when assessed by conventional culture, metabolic dye and live dead qPCR. These biofilms were both structurally complex and compositionally dynamic in response to topical therapy, so when treated with either chlorhexidine or povidone iodine, principal component analysis revealed that the 3-D cellulose model was minimally impacted compared to the simple substratum model. This study highlights the importance of biofilm substratum and inclusion of relevant polymicrobial and inter-kingdom components, as these impact penetration and efficacy of topical antiseptics

Synthesis of Molybdenum and Tungsten Alkylidene Complexes That Contain Sterically Demanding Arenethiolate Ligands

Imido alkylidene complexes of Mo and W and oxo alkylidene complexes of W that contain thiophenoxide ligands of the type S-2,3,5,6-Ph[subscript 4]C[subscript 6]H (STPP) and S-2,6-(mesityl)[subscript 2]C[subscript 6]H[subscript 3] (SHMT = S-hexamethylterphenyl) have been prepared in order to compare their metathesis activity with that of the analogous phenoxide complexes. All thiolate complexes were significantly slower (up to ∼10× slower) for the metathesis homocoupling of 1-octene or polymerization of 2,3-dicarbomethoxynorbornene, and none of them was Z-selective. The slower rates could be attributed to the greater σ-donating ability of a thiophenoxide versus the analogous phenoxide and consequently a higher electron density at the metal in the thiophenoxide complexes.National Institutes of Health (U.S.) (Grant GM-59426

Earthquake science in resilient societies

Earthquake science is critical in reducing vulnerability to a broad range of seismic hazards. Evidenceâ based studies drawing from several branches of the Earth sciences and engineering can effectively mitigate losses experienced in earthquakes. Societies that invest in this research have lower fatality rates in earthquakes and can recover more rapidly. This commentary explores the scientific pathways through which earthquakeâ resilient societies are developed. We highlight recent case studies of evidenceâ based decision making and how modern research is improving the way societies respond to earthquakes.Key PointsThe level of seismic risk depends in part on societal investment in earthquake scienceMultidisciplinary investigations involving earthquake scientists and engineers greatly reduce casualties in earthquakesRecent examples highlight the utility of earthquake science in building resilient societies and the need for further research to reduce seismic riskPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137197/1/tect20552_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137197/2/tect20552.pd

In-vitro and in-vivo evidence for uncoupling of BCR internalization and signaling in chronic lymphocytic leukemia

B-cell receptor activation, occurring within lymph nodes, plays a key role in the pathogenesis of chronic lymphocytic leukemia and is linked to prognosis. As well as activation of downstream signaling, receptor ligation triggers internalization, transit to acidified endosomes and degradation of ligand-receptor complexes. In the present study we investigated the relationship between these two processes in normal and leukemic B-cells. We found that leukemic B-cells, particularly anergic cases lacking the capacity to initiate downstream signaling, internalize and accumulate ligand in acidified endosomes more efficiently than normal B-cells. Furthermore, ligation of either surface CD79B, a Bcell receptor component required for downstream signaling, or surface IgM by cognate agonistic antibody, showed that the two molecules internalize independently of each other in leukemic but not normal B-cells. Since association with surface CD79B is required for surface retention of IgM, this suggests that uncoupling of B-cell receptor internalization from signaling may be due to dissociation of these two molecules in leukemic cells. Comparison of lymph node with peripheral blood cells from chronic lymphocytic leukemia patients showed that, despite recent B-cell receptor activation, lymph node B-cells expressed higher levels of surface IgM. This surprising finding suggests that the B-cell receptors of lymph node and peripheral blood derived leukemic cells might be functionally distinct. Finally, long-term therapy with the Bruton’s tyrosine kinase inhibitors ibrutinib or acalabrutinib resulted in a switch to an anergic pattern of B-cell receptor function with reduced signaling capacity, surface IgM expression and more efficient internalization

The TEMPO Survey I: Predicting Yields of the Transiting Exosatellites, Moons, and Planets from a 30-day Survey of Orion with the Nancy Grace Roman Space Telescope

We present design considerations for the Transiting Exosatellites, Moons, and Planets in Orion (TEMPO) Survey with the Nancy Grace Roman Space Telescope. This proposed 30-day survey is designed to detect a population of transiting extrasolar satellites, moons, and planets in the Orion Nebula Cluster (ONC). The young (1-3 Myr), densely-populated ONC harbors about a thousand bright brown dwarfs (BDs) and free-floating planetary-mass objects (FFPs). TEMPO offers sufficient photometric precision to monitor FFPs with ${\rm M}\geq1{\rm M}_{\rm J}$ for transiting satellites. The survey is also capable of detecting FFPs down to sub-Saturn masses via direct imaging, although follow-up confirmation will be challenging. TEMPO yield estimates include 14 (3-22) exomoons/satellites transiting FFPs and 54 (8-100) satellites transiting BDs. Of this population, approximately $50\%$ of companions would be "super-Titans" (Titan to Earth mass). Yield estimates also include approximately $150$ exoplanets transiting young Orion stars, of which $>50\%$ will orbit mid-to-late M dwarfs and approximately ten will be proto-habitable zone, terrestrial ($0.1{\rm M}_{\oplus} - 5{\rm M}_{\oplus}$) exoplanets. TEMPO would provide the first census demographics of small exosatellites orbiting FFPs and BDs, while simultaneously offering insights into exoplanet evolution at the earliest stages. This detected exosatellite population is likely to be markedly different from the current census of exoplanets with similar masses (e.g., Earth-mass exosatellites that still possess H/He envelopes). Although our yield estimates are highly uncertain, as there are no known exoplanets or exomoons analogous to these satellites, the TEMPO survey would test the prevailing theories of exosatellite formation and evolution, which limit the certainty surrounding detection yields.Comment: Submitted to PAS