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Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen that forms robust biofilms in the different niches it occupies. Numerous physiological adaptations are required as this organism shifts from soil or aquatic environments to a host-associated lifestyle. While many conditions differ between these niches, temperature shifts are a factor that can contribute to physiological stress during this transition. To understand how temperature impacts biofilm formation in this pathogen, we used proteomic and transcriptomic tools to elucidate physiological responses in environment-relevant vs. host-relevant temperatures. These studies uncovered differential expression of various proteins including a phage protein that is associated with the EPS matrix in P. aeruginosa. This filamentous phage was induced at host temperatures and was required for full biofilm-forming capacity specifically at human body temperature. These data highlight the importance of temperature shift in biofilm formation and suggest bacteriophage proteins could be a possible therapeutic target in biofilm-associated infections.The lipid-enveloped influenza C virus contains a single surface glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, that mediates receptor binding, receptor destruction, and membrane fusion at the low pH of the endosome. Here we apply electron cryotomography and subtomogram averaging to describe the structural basis for hexagonal lattice formation by HEF on the viral surface. TAPI-1 The conformation of the glycoprotein in situ is distinct from the structure of the isolated trimeric ectodomain, showing that a splaying of the membrane distal domains is required to mediate contacts that form the lattice. The splaying of these domains is also coupled to changes in the structure of the stem region which is involved in membrane fusion, thereby linking HEF's membrane fusion conformation with its assembly on the virus surface. The glycoprotein lattice can form independent of other virion components but we show a major role for the matrix layer in particle formation.Break-off of part of the down-going plate during continental collision occurs due to tensile stresses built-up between the deep and shallow slab, for which buoyancy is increased because of continental-crust subduction. Break-off governs the subsequent orogenic evolution but real-time observations are rare as it happens over geologically short times. Here we present a finite-frequency tomography, based on jointly inverted local and remote earthquakes, for the Hindu Kush in Afghanistan, where slab break-off is ongoing. We interpret our results as crustal subduction on top of a northwards-subducting Indian lithospheric slab, whose penetration depth increases along-strike while thinning and steepening. This implies that break-off is propagating laterally and that the highest lithospheric stretching rates occur during the final pinching-off. In the Hindu Kush crust, earthquakes and geodetic data show a transition from focused to distributed deformation, which we relate to a variable degree of crust-mantle coupling presumably associated with break-off at depth.Organic synthesis remains a major challenge in drug discovery. Although a plethora of machine learning models have been proposed as solutions in the literature, they suffer from being opaque black-boxes. It is neither clear if the models are making correct predictions because they inferred the salient chemistry, nor is it clear which training data they are relying on to reach a prediction. This opaqueness hinders both model developers and users. In this paper, we quantitatively interpret the Molecular Transformer, the state-of-the-art model for reaction prediction. We develop a framework to attribute predicted reaction outcomes both to specific parts of reactants, and to reactions in the training set. Furthermore, we demonstrate how to retrieve evidence for predicted reaction outcomes, and understand counterintuitive predictions by scrutinising the data. Additionally, we identify Clever Hans predictions where the correct prediction is reached for the wrong reason due to dataset bias. We present a new debiased dataset that provides a more realistic assessment of model performance, which we propose as the new standard benchmark for comparing reaction prediction models.Most of Earth's fresh surface water is consolidated in just a few of its largest lakes, and because of their unique response to environmental conditions, lakes have been identified as climate change sentinels. While the response of lake surface water temperatures to climate change is well documented from satellite and summer in situ measurements, our understanding of how water temperatures in large lakes are responding at depth is limited, as few large lakes have detailed long-term subsurface observations. We present an analysis of three decades of high frequency (3-hourly and hourly) subsurface water temperature data from Lake Michigan. This unique data set reveals that deep water temperatures are rising in the winter and provides precise measurements of the timing of fall overturn, the point of minimum temperature, and the duration of the winter cooling period. Relationships from the data show a shortened winter season results in higher subsurface temperatures and earlier onset of summer stratification. Shifts in the thermal regimes of large lakes will have profound impacts on the ecosystems of the world's surface freshwater.Artificial light at night has rapidly spread around the globe over the last decades. Evidence is increasing that it has adverse effects on the behavior, physiology, and survival of animals and plants with consequences for species interactions and ecosystem functioning. For example, artificial light at night disrupts plant-pollinator interactions at night and this can have consequences for the plant reproductive output. By experimentally illuminating natural plant-pollinator communities during the night using commercial street-lamps we tested whether light at night can also change interactions of a plant-pollinator community during daytime. Here we show that artificial light at night can alter diurnal plant-pollinator interactions, but the direction of the change depends on the plant species. We conclude that the effect of artificial light at night on plant-pollinator interactions is not limited to the night, but can also propagate to the daytime with so far unknown consequences for the pollinator community and the diurnal pollination function and services they provide.Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. link2 Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.More than half of current coal power capacity is in China. A key strategy for meeting China's 2060 carbon neutrality goal and the global 1.5 °C climate goal is to rapidly shift away from unabated coal use. Here we detail how to structure a high-ambition coal phaseout in China while balancing multiple national needs. We evaluate the 1037 currently operating coal plants based on comprehensive technical, economic and environmental criteria and develop a metric for prioritizing plants for early retirement. We find that 18% of plants consistently score poorly across all three criteria and are thus low-hanging fruits for rapid retirement. We develop plant-by-plant phaseout strategies for each province by combining our retirement algorithm with an integrated assessment model. With rapid retirement of the low-hanging fruits, other existing plants can operate with a 20- or 30-year minimum lifetime and gradually reduced utilization to achieve the 1.5 °C or well-below 2 °C climate goals, respectively, with complete phaseout by 2045 and 2055.When a very strong light field is applied to a molecule an electron can be ejected by tunneling. In order to quantify the time-resolved dynamics of this ionization process, the concept of the Wigner time delay can be used. The properties of this process can depend on the tunneling direction relative to the molecular axis. Here, we show experimental and theoretical data on the Wigner time delay for tunnel ionization of H2 molecules and demonstrate its dependence on the emission direction of the electron with respect to the molecular axis. We find, that the observed changes in the Wigner time delay can be quantitatively explained by elongated/shortened travel paths of the emitted electrons, which occur due to spatial shifts of the electrons' birth positions after tunneling. Our work provides therefore an intuitive perspective towards the Wigner time delay in strong-field ionization.Biosecurity interception records are crucial data underlying efforts to predict and manage pest and pathogen introductions. Here we present a dataset containing information on imported plant products inspected by the South African Department of Agriculture's laboratories between 1994 and 2019 and the contaminant organisms found on them. Samples were received from border inspectors as either propagation material (e.g. plants) or material for immediate use (e.g. fruit). Material for immediate use was further divided into two sample categories, depending on if contaminants were seen/suspected by the border official or not intervention or audit samples. The final dataset consists of 25,279 records, of which 30% tested positive (i.e. had at least one contaminant) and 13% had multiple contaminants. link3 Of the 13,731 recorded contaminants, fungi (41%), mites (37%) and insects (19%) were most common. This dataset provides insight into the suite of taxa transported along the plant import pathway and provides an important resource for analyses of contaminant organisms in international trade, which can inform strategies for risk assessment, pathway management and biosecurity protocols.Bone tumors, especially those in osteosarcoma, usually occur in adolescents. The standard clinical treatment includes chemotherapy, surgical therapy, and radiation therapy. Unfortunately, surgical resection often fails to completely remove the tumor, which is the main cause of postoperative recurrence and metastasis, resulting in a high mortality rate. Moreover, bone tumors often invade large areas of bone, which cannot repair itself, and causes a serious effect on the quality of life of patients. Thus, bone tumor therapy and bone regeneration are challenging in the clinic. Herein, this review presents the recent developments in bifunctional biomaterials to achieve a new strategy for bone tumor therapy. The selected bifunctional materials include 3D-printed scaffolds, nano/microparticle-containing scaffolds, hydrogels, and bone-targeting nanomaterials. Numerous related studies on bifunctional biomaterials combining tumor photothermal therapy with enhanced bone regeneration were reviewed. Finally, a perspective on the future development of biomaterials for tumor therapy and bone tissue engineering is discussed.
Here's my website: https://www.selleckchem.com/products/tapi-1.html
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