Plastic usage by microbes as a carbon source is a promising strategy to increase the recycling quota. 1,4‐butanediol (BDO) is a common monomer derived from polyesters and polyurethanes. In this ...study, Ustilago trichophora was found to be an efficient cell‐factory to valorize BDO. To investigate product formation by U. trichophora, we refined the traditional ion exclusion liquid chromatography method by examining eluent, eluent concentrations, oven temperatures, and organic modifiers to make the chromatography compatible with mass spectrometry. An LC‐UV/RI‐MS2 method is presented here to identify and quantify extracellular metabolites in the cell cultures. With this method, we successfully identified that U. trichophora secreted malic acid, succinic acid, erythritol, and mannitol into the culture medium. Adaptive laboratory evolution followed by medium optimization significantly improved U. trichophora growth on BDO and especially malic acid production. Overall, the carbon yield on the BDO substrate was approximately 33% malic acid. This study marks the first report of a Ustilaginaceae fungus capable of converting BDO into versatile chemical building blocks. Since U. trichophora is not genetically engineered, it is a promising microbial host to produce malic acid from BDO, thereby contributing to the development of the envisaged sustainable bioeconomy.
Ustilago trichophora was found to be able to degrade BDO, one of the plastic monomers from the depolymerization process of polyurethane (PU) or polyesters (i.e., PBS, PBAT). Using a newly developed IELC‐UV/RI‐MS/MS method, extracellular metabolites were identified as malic acid, succinic acid, erythritol, and mannitol. Adaptive laboratory evolution followed by medium optimization significantly improved U. trichophora growth on BDO and especially malic acid production, with a substrate‐to‐product yield of 33%.
Seed mucilage polysaccharide production, storage and release in Plantagoovata is strikingly different to that of the model plant Arabidopsis. We have used microscopy techniques to track the ...development of mucilage secretory cells and demonstrate that mature P.ovata seeds do not have an outer intact cell layer within which the polysaccharides surround internal columellae. Instead, dehydrated mucilage is spread in a thin homogenous layer over the entire seed surface and upon wetting expands directly outwards, away from the seed. Observing mucilage expansion in real time combined with compositional analysis allowed mucilage layer definition and the roles they play in mucilage release and architecture upon hydration to be explored. The first emergent layer of hydrated mucilage is rich in pectin, extremely hydrophilic, and forms an expansion front that functions to ‘jumpstart’ hydration and swelling of the second layer. This next layer, comprising the bulk of the expanded seed mucilage, is predominantly composed of heteroxylan and appears to provide much of the structural integrity. Our results indicate that the synthesis, deposition, desiccation, and final storage position of mucilage polysaccharides must be carefully orchestrated, although many of these processes are not yet fully defined and vary widely between myxospermous plant species.
The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B ...cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell-FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell.
Mixed reality for robotics Honig, Wolfgang; Milanes, Christina; Scaria, Lisa ...
2015 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS),
09/2015
Conference Proceeding
Mixed Reality can be a valuable tool for research and development in robotics. In this work, we refine the definition of Mixed Reality to accommodate seamless interaction between physical and virtual ...objects in any number of physical or virtual environments. In particular, we show that Mixed Reality can reduce the gap between simulation and implementation by enabling the prototyping of algorithms on a combination of physical and virtual objects, including robots, sensors, and humans. Robots can be enhanced with additional virtual capabilities, or can interact with humans without sharing physical space. We demonstrate Mixed Reality with three representative experiments, each of which highlights the advantages of our approach. We also provide a testbed for Mixed Reality with three different virtual robotics environments in combination with the Crazyflie 2.0 quadcopter.
mRNA lipid nanoparticle (LNP) vaccines would be useful during an influenza virus pandemic since they can be produced rapidly and do not require the generation of egg-adapted vaccine seed stocks. ...Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating at unprecedently high levels in wild and domestic birds and have the potential to adapt to humans. Here, we generate an mRNA lipid nanoparticle (LNP) vaccine encoding the hemagglutinin (HA) glycoprotein from a clade 2.3.4.4b H5 isolate. The H5 mRNA-LNP vaccine elicits strong T cell and antibody responses in female mice, including neutralizing antibodies and broadly-reactive anti-HA stalk antibodies. The H5 mRNA-LNP vaccine elicits antibodies at similar levels compared to whole inactivated vaccines in female mice with and without prior H1N1 exposures. Finally, we find that the H5 mRNA-LNP vaccine is immunogenic in male ferrets and prevents morbidity and mortality of animals following 2.3.4.4b H5N1 challenge. Together, our data demonstrate that a monovalent mRNA-LNP vaccine expressing 2.3.4.4b H5 is immunogenic and protective in pre-clinical animal models.
To assess the presence and distribution of the
sul genes (
sul1,
sul2, and
sul3) and plasmids in human-mediated environments of north Vietnam, we examined a total of 127 sulfonamide-resistant (SR) ...bacterial isolates from four shrimp ponds (HNAQs), a city canal (HNCs) and three fish ponds that received wastewater directly from swine farms (HNPs). Results from the SR isolates revealed that
sul genes were most frequently detected in the HNPs (92.0%), followed by HNCs (72.0%), and the HNAQs (43.0%). Among the
sul genes detected,
sul1 was the most prevalent gene in all three environments (57.0, 33.0 and 60.0% in HNPs, HNAQs, and HNCs, respectively) followed by
sul2 (51.0, 19.0, and 20.0%, respectively) and
sul3 (14.0, 6.0, and 8.0%, respectively). All combinations of paired different
sul genes were detected, with the combination between
sul1 and
sul2 being the most frequent in all three environments (20.0, 8.0, and 8.0% in HNPs, HNAQs, and HNCs, respectively). The combination of three
sul genes was detected at low frequencies (2–3%) in the HNPs and HNAQs, and was absent in the HNCs. The
sul genes were more frequently located on the chromosome than on plasmids. The identification of SR isolates positive for the
sul genes and plasmids showed that
Acinetobacter was the most dominant. Our study revealed that the
sul genes were common in SR bacteria from the aquatic environments we examined from northern Vietnam. Wastewater from swine farms might be “hot spots” of the
sul genes and plasmids and may be reservoirs for the exchange of the
sul genes among bacteria.
Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta-analysis has focused on minor ischemic stroke alone. The objective was to evaluate ...the pooled proportion of 90-day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5.
Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90-day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random-effects meta-analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90-day stroke recurrence was 8.6% (95% CI, 6.5-10.7), reducing by 0.60% (95% CI, 0.09-1.1;
=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5-8.0) when compared with non-dual antiplatelet trial arms (7.2%, 95% CI, 4.7-9.6) and observational studies 10.6% (95% CI, 7.0-14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference - score ≤3: 8.6% (95% CI, 6.0-11.1), score ≤4: 8.4% (95% CI, 6.1-10.6), as did excluding studies with n<500%-7.3% (95% CI, 5.5-9.0).
The risk of recurrence after minor ischemic stroke is declining over time but remains important.
The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line ...antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer's and Huntington's disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A
(GAS), methicillin-resistant
(MRSA), and vancomycin-resistant
(VRE). We were unable to select for mutants resistant to PBT2-zinc treatment. While ineffective alone against resistant bacteria, several clinically relevant antibiotics act synergistically with PBT2-zinc to enhance killing of these Gram-positive pathogens. These data represent a new paradigm whereby disruption of bacterial metal homeostasis reverses antibiotic-resistant phenotypes in a number of priority human bacterial pathogens.
The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant
and vancomycin-resistant
are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore,
, a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, "On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you."
JCO
Sacituzumab govitecan (SG), a first-in-class anti-trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of ...physician's choice TPC) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study.Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression. Final efficacy secondary end point analyses and post hoc analyses of outcomes stratified by Trop-2 expression and human epidermal growth factor receptor 2 status are reported. Updated safety analyses are provided.In this final analysis, SG (n = 267) improved median progression-free survival (PFS; 4.8
1.7 months; hazard ratio (HR), 0.41 95% CI, 0.33 to 0.52) and median overall survival (OS; 11.8
6.9 months; HR, 0.51 95% CI, 0.42 to 0.63) over TPC (n = 262). SG improved PFS over TPC in each Trop-2 expression quartile (n = 168); a trend was observed for improved OS across quartiles. Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups.These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.
The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. ...While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect hPSC-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide ChIP enrichment and mechanistic studies show that p38 MAPK-mediated CEBPD upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in MSCs exerts a negative regulatory effect on osteogenesis through a similar mechanism. ChIP-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment.
•Systematic transcriptome profiling of hPSC-derived osteoblasts.•Discovery of CORIN and SDC1 as the crucial surface membrane proteins for bone development.•CORIN and SDC1 regulate CEPBD-mediated osteogenesis via p38 MAPK.•Multi-omics analysis reveals CEBPD-regulated osteoblast gene networks.
PDF
