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15 result(s) for "Lück, Rebecca"
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Genetic tools for the redirection of the central carbon flow towards the production of lactate in the human gut bacterium Phocaeicola (Bacteroides) vulgatus
Species of the genera Bacteroides and Phocaeicola play an important role in the human colon. The organisms contribute to the degradation of complex heteropolysaccharides to small chain fatty acids, which are in part utilized by the human body. Furthermore, these organisms are involved in the synthesis of vitamins and other bioactive compounds. Of special interest is Phocaeicola vulgatus , originally classified as a Bacteroides species, due to its abundance in the human intestinal tract and its ability to degrade many plant-derived heteropolysaccharides. We analyzed different tools for the genetic modification of this microorganism, with respect to homologous gene expression of the ldh gene encoding a D-lactate dehydrogenase (LDH). Therefore, the ldh gene was cloned into the integration vector pMM656 and the shuttle vector pG106 for homologous gene expression in P. vulgatus . We determined the ldh copy number, transcript abundance, and the enzyme activity of the wild type and the mutants. The strain containing the shuttle vector showed an approx. 1500-fold increase in the ldh transcript concentration and an enhanced LDH activity that was about 200-fold higher compared to the parental strain. Overall, the proportion of lactate in the general catabolic carbon flow increased from 2.9% (wild type) to 28.5% in the LDH-overproducing mutant. This approach is a proof of concept, verifying the genetic accessibility of P. vulgatus and could form the basis for targeted genetic optimization. Key points • A lactate dehydrogenase was overexpressed in Phocaeicola (Bacteroides) vulgatus. • The ldh transcript abundance and the LDH activity increased sharply in the mutant. • The proportion of lactate in the catabolic carbon flow increased to about 30%.
Enhancing Autonomous Vehicle Safety in Cold Climates by Using a Road Weather Model: Safely Avoiding Unnecessary Operational Design Domain Exits
This study investigates the use of a road weather model (RWM) as a virtual sensing technique to assist autonomous vehicles (AVs) in driving safely, even in challenging winter weather conditions. In particular, we investigate how the AVs can remain within their operational design domain (ODD) for a greater duration and minimize unnecessary exits. As the road surface temperature (RST) is one of the most critical variables for driving safety in winter weather, we explore the use of the vehicle’s air temperature (AT) sensor as an indicator of RST. Data from both Road Weather Information System (RWIS) stations and vehicles measuring AT and road conditions were used. Results showed that using only the AT sensor as an indicator of RST could result in a high number of false warnings, but the accuracy improved significantly with the use of an RWM to model the RST. ROC-curve analysis resulted in an AUC value of 0.917 with the AT sensor and 0.985 with the RWM, while the true positive rate increased from 67% to 94%. The study also highlights the limitations of relying on dashboard cameras to detect slippery driving conditions, as it may not be accurate enough to distinguish between, for example, wet and icy road conditions. As winter maintenance often prevents slippery roads, the vehicles often measured wet or moist roads, despite RST < 0°C. Our calculations indicate that the vehicle should be able to detect 93% of slippery occasions but the rate of false warnings will be as high as 73%, if using a dashboard camera along with the AT sensor. There are clear benefits of using a RWM to improve road safety and reduce the risk of accidents due to slippery conditions, allowing AVs to safely extend their time within their ODD. The findings of this study provide valuable insights for the development of AVs and their response to slippery road conditions.
Genetic optimization of the human gut bacterium Phocaeicola vulgatus for enhanced succinate production
The demand for sustainably produced bulk chemicals is constantly rising. Succinate serves as a fundamental component in various food, chemical, and pharmaceutical products. Succinate can be produced from sustainable raw materials using microbial fermentation and enzyme-based technologies. Bacteroides and Phocaeicola species, widely distributed and prevalent gut commensals, possess enzyme sets for the metabolization of complex plant polysaccharides and synthesize succinate as a fermentative end product. This study employed novel molecular techniques to enhance succinate yields in the natural succinate producer Phocaeicola vulgatus by directing the metabolic carbon flow toward succinate formation. The deletion of the gene encoding the methylmalonyl-CoA mutase (Δ mcm , bvu_0309-0310 ) resulted in a 95% increase in succinate production, as metabolization to propionate was effectively blocked. Furthermore, deletion of genes encoding the lactate dehydrogenase (Δ ldh , bvu_2499 ) and the pyruvate:formate lyase (Δ pfl , bvu_2880 ) eliminated the formation of fermentative end products lactate and formate. By overproducing the transketolase (TKT, BVU_2318) in the triple deletion mutant, succinate production increased from 3.9 mmol/g dry weight in the wild type to 10.9 mmol/g dry weight. Overall, succinate yield increased by 180% in the new mutant strain P. vulgatus Δ mcm Δ ldh Δ pfl pG106_ tkt relative to the parent strain. This approach is a proof of concept, verifying the genetic accessibility of P. vulgatus , and forms the basis for targeted genetic optimization. The increase of efficiency highlights the huge potential of P. vulgatus as a succinate producer with applications in sustainable bioproduction processes. Key points • Deleting methylmalonyl-CoA mutase gene in P. vulgatus doubled succinate production • Triple deletion mutant with transketolase overexpression increased succinate yield by 180% • P. vulgatus shows high potential for sustainable bulk chemical production via genetic optimization
Das unterschätzte biotechnologische Potenzial der Darmmikrobiota
The human gut microbiota harbors untapped potential for biotechnological applications. Within the phylum of Bacteroidota, Phocaeicola vulgatus stands out as a promising candidate for sustainable production of key platform chemicals like succinate. However, genetic engineering of Phocaeicola sp. remains challenging due to its intricate molecular landscape. This study lays the groundwork for manipulating the central carbon pathways in Phocaeicola vulgatus , offering insights into overcoming genetic hurdles for increased succinate yields.
Das unterschätzte biotechnologische Potenzial der Darmmikrobiota
The human gut microbiota harbors untapped potential for biotechnological applications. Within the phylum of Bacteroidota, Phocaeicola vulgatus stands out as a promising candidate for sustainable production of key platform chemicals like succinate. However, genetic engineering of Phocaeicola sp. remains challenging due to its intricate molecular landscape. This study lays the groundwork for manipulating the central carbon pathways in Phocaeicola vulgatus, offering insights into overcoming genetic hurdles for increased succinate yields.
Pollinators, pests, and predators: Recognizing ecological trade-offs in agroecosystems
Ecological interactions between crops and wild animals frequently result in increases or declines in crop yield. Yet, positive and negative interactions have mostly been treated independently, owing partly to disciplinary silos in ecological and agricultural sciences. We advocate a new integrated research paradigm that explicitly recognizes cost-benefit trade-offs among animal activities and acknowledges that these activities occur within socialecological contexts. Support for this paradigm is presented in an evidence-based conceptual model structured around five evidence statements highlighting emerging trends applicable to sustainable agriculture. The full range of benefits and costs associated with animal activities in agroecosystems cannot be quantified by focusing on single species groups, crops, or systems. Management of productive agroecosystems should sustain cycles of ecological interactions between crops and wild animals, not isolate these cycles from the system. Advancing this paradigm will therefore require integrated studies that determine net returns of animal activity in agroecosystems.
Cost-benefit trade-offs of bird activity in apple orchards
Birds active in apple orchards in south–eastern Australia can contribute positively (e.g., control crop pests) or negatively (e.g., crop damage) to crop yields. Our study is the first to identify net outcomes of these activities, using six apple orchards, varying in management intensity, in south–eastern Australia as a study system. We also conducted a predation experiment using real and artificial codling moth ( Cydia pomonella ) larvae (a major pest in apple crops). We found that: (1) excluding birds from branches of apple trees resulted in an average of 12.8% more apples damaged by insects; (2) bird damage to apples was low (1.9% of apples); and (3) when trading off the potential benefits (biological control) with costs (bird damage to apples), birds provided an overall net benefit to orchard growers. We found that predation of real codling moth larvae was higher than for plasticine larvae, suggesting that plasticine prey models are not useful for inferring actual predation levels. Our study shows how complex ecological interactions between birds and invertebrates affect crop yield in apples, and provides practical strategies for improving the sustainability of orchard systems.
Alzheimer’s disease-associated (hydroxy)methylomic changes in the brain and blood
Background Late-onset Alzheimer’s disease (AD) is a complex multifactorial affliction, the pathogenesis of which is thought to involve gene-environment interactions that might be captured in the epigenome. The present study investigated epigenome-wide patterns of DNA methylation (5-methylcytosine, 5mC) and hydroxymethylation (5-hydroxymethylcytosine, 5hmC), as well as the abundance of unmodified cytosine (UC), in relation to AD. Results We identified epigenetic differences in AD patients ( n  = 45) as compared to age-matched controls ( n  = 35) in the middle temporal gyrus, pertaining to genomic regions close to or overlapping with genes such as OXT (− 3.76% 5mC, p Šidák  = 1.07E−06), CHRNB1 (+ 1.46% 5hmC, p Šidák  = 4.01E−04), RHBDF2 (− 3.45% UC, p Šidák  = 4.85E−06), and C3 (− 1.20% UC, p Šidák  = 1.57E−03). In parallel, in an independent cohort, we compared the blood methylome of converters to AD dementia ( n  = 54) and non-converters ( n  = 42), at a preclinical stage. DNA methylation in the same region of the OXT promoter as found in the brain was found to be associated with subsequent conversion to AD dementia in the blood of elderly, non-demented individuals (+ 3.43% 5mC, p Šidák  = 7.14E−04). Conclusions The implication of genome-wide significant differential methylation of OXT , encoding oxytocin, in two independent cohorts indicates it is a promising target for future studies on early biomarkers and novel therapeutic strategies in AD.
Virus infection mediates the effects of elevated CO2 on plants and vectors
Atmospheric carbon dioxide (CO 2 ) concentration has increased significantly and is projected to double by 2100. To increase current food production levels, understanding how pests and diseases respond to future climate driven by increasing CO 2 is imperative. We investigated the effects of elevated CO 2 (eCO 2 ) on the interactions among wheat (cv. Yitpi), Barley yellow dwarf virus and an important pest and virus vector, the bird cherry-oat aphid ( Rhopalosiphum padi ), by examining aphid life history, feeding behavior and plant physiology and biochemistry. Our results showed for the first time that virus infection can mediate effects of eCO 2 on plants and pathogen vectors. Changes in plant N concentration influenced aphid life history and behavior and N concentration was affected by virus infection under eCO 2 . We observed a reduction in aphid population size and increased feeding damage on noninfected plants under eCO 2 but no changes to population and feeding on virus-infected plants irrespective of CO 2 treatment. We expect potentially lower future aphid populations on noninfected plants but no change or increased aphid populations on virus-infected plants therefore subsequent virus spread. Our findings underscore the complexity of interactions between plants, insects and viruses under future climate with implications for plant disease epidemiology and crop production.
Alcohol and Immunology: Mechanisms of multi-organ damage. Summary of the 2022 alcohol and Immunology research interest group (AIRIG) meeting
On October 26th, 2022 the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Hawaii. The 2022 meeting focused broadly on the immunological consequences of acute, chronic, and prenatal alcohol exposure and how these contribute to damage in multiple organs and tissues. These included alcohol-induced neuroinflammation, impaired lung immunity, intestinal dysfunction, and decreased anti-microbial and anti-viral responses. In addition, research presented covered multiple pathways behind alcohol-induced cellular dysfunction, including mitochondrial metabolism, cellular bioenergetics, gene regulation, and epigenetics. Finally, the work presented highlighted potential biomarkers and novel avenues of treatment for alcohol-induced organ damage. •Alcohol disrupts immune cell bioenergetics and metabolism.•Ethanol changes epigenetic processes that alter neurogenesis in the brain.•Ethanol stimulates changes in the gut that contribute to neuroinflammation after injury.•Ethanol-induced intestinal dysfunction is reversed by rIL-27 or short chain fatty acids.•The age at which alcohol exposure occurs influences the inflammatory response.