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Polymer electrolyte membrane fuel cells (PEMFCs) are an important enabler of the nascent hydrogen economy. However, due to the reliance on precious metal catalysts like platinum, reducing the cost and broad penetration of PEMFCs beyond vehicle application remains a challenge. In this respect, alternative non‐precious metal catalysts and other carbon‐based catalysts remain the holy grail toward advanced low‐cost PEMFC. This review summarizes recent progress along the development of non‐precious catalysts and their performance under PEMFC operation. Critical factors such as the activity, stability, and durability of non‐precious metal catalysts and their associated mechanisms including the paths leading to degradation are discussed. Ultimately, the review concludes by highlighting the impressive activity and potential of NPM catalysts and the areas of focus to enable the translation of non‐precious catalysts to commercially viable PEMFC systems. [ABSTRACT FROM AUTHOR]

The thioredoxin (Trx) system, found universally, is responsible for the regeneration of reversibly oxidized protein thiols in living cells. This system is made up of a Trx and a Trx reductase, and it plays a central role in maintaining thiol‐based redox homeostasis by reducing oxidized protein thiols, such as disulfide bonds in proteins. Some Trxs also possess a chaperone function that is independent of thiol‐disulfide exchange, in addition to their thiol‐disulfide reductase activity. These two activities of the Trx system are involved in numerous physiological processes in bacteria. This review describes the diverse physiological roles of the Trx system that have emerged throughout bacterial evolution. The Trx system is essential for responding to oxidative and nitrosative stress. Beyond this primary function, the Trx system also participates in redox regulation and signal transduction, and in controlling metabolism, motility, biofilm formation, and virulence. This range of functions has evolved alongside the diversity of bacterial lifestyles and their specific constraints. This evolution can be characterized by the multiplication of the systems and by the specialization of cofactors or targets to adapt to the constraints of atypical lifestyles, such as photosynthesis, insect endosymbiosis, or spore‐forming bacteria. [ABSTRACT FROM AUTHOR]

Executive summary: Microbes are all pervasive in their distribution and influence on the functioning and well‐being of humans, life in general and the planet. Microbially‐based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision‐makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative–the IMiLI–is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence‐based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner‐centric, not academic microbiology‐centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators–learners. As such, they will collect and analyse feedback from the end‐users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators–learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships–a global societally relevant microbiology education ecosystem–in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well‐being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us–individuals/communities/nations/the human world–and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. Here, we present: our concept of how microbiology literacy may be achieved and the rationale underpinning it;the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision‐making; andthe key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner‐centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091–1111). Importantly, although the primary target of the freely available (CC BY‐NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity‐driven, web‐based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge. [ABSTRACT FROM AUTHOR]

Immobilization of stimulus‐responsive systems on solid surfaces is beneficial for controlled signal transmission and adaptive behavior while allowing the characterization of the functional interface with high sensitivity and high spatial resolution. Positioning of the stimuli‐responsive units with nanometer‐scale precision across the adaptive surface remains one of the bottlenecks in the extraction of cooperative function. Nanoscale organization, cooperativity, and amplification remain key challenges in bridging the molecular and the macroscopic worlds. Here we report on the design, synthesis, and scanning tunneling microscopy (STM) characterization of overcrowded alkene photoswitches merged in self‐assembled networks physisorbed at the solid‐liquid interface. A detailed anchoring strategy that ensures appropriate orientation of the switches with respect to the solid surface through the use of bis‐urea groups is presented. We implement a co‐assembly strategy that enables the merging of the photoswitches within physisorbed monolayers of structurally similar 'spacer' molecules. The self‐assembly of the individual components and the co‐assemblies was examined in detail using (sub)molecular resolution STM which confirms the robust immobilization and controlled orientation of the photoswitches within the spacer monolayers. The experimental STM data is supported by detailed molecular mechanics (MM) simulations. Different designs of the switches and the spacers were investigated which allowed us to formulate guidelines that enable the precise organization of the photoswitches in crystalline physisorbed self‐assembled molecular networks. [ABSTRACT FROM AUTHOR]

Microbes are powerful upgraders, able to convert simple substrates to nutritional metabolites at rates and yields surpassing those of higher organisms by a factor of 2 to 10. A summary table highlights the superior efficiencies of a whole array of microbes compared to conventionally farmed animals and insects, converting nitrogen and organics to food and feed. Aiming at the most resource‐efficient class of microbial proteins, deploying the power of open microbial communities, coined here as 'symbiotic microbiomes' is promising. For instance, a production train of interest is to develop rumen‐inspired technologies to upgrade fibre‐rich substrates, increasingly available as residues from emerging bioeconomy initiatives. Such advancements offer promising perspectives, as currently only 5%–25% of the available cellulose is recovered by ruminant livestock systems. While safely producing food and feed with open cultures has a long‐standing tradition, novel symbiotic fermentation routes are currently facing much higher market entrance barriers compared to axenic fermentation. Our global society is at a pivotal juncture, requiring a shift towards food production systems that not only embrace the environmental and economic sustainability but also uphold ethical standards. In this context, we propose to re‐examine the place of spontaneous or natural microbial consortia for safe future food and feed biotech developments, and advocate for intelligent regulatory practices. We stress that reconsidering symbiotic microbiomes is key to achieve sustainable development goals and defend the need for microbial biotechnology literacy education. [ABSTRACT FROM AUTHOR]

We consider the maximum chromatic number of hypergraphs consisting of cliques that have pairwise small intersections. Designs of the appropriate parameters produce optimal constructions, but these are generally known to exist only when the number of cliques is exponential in the clique size (Glock, Kühn, Lo, and Osthus, Mem. Amer. Math. Soc. 284 (2023) v+131 pp; Keevash, Preprint; Rödl, Eur. J. Combin. 6 (1985) 69–78). We construct near designs where the number of cliques is polynomial in the clique size, and show that they have large chromatic number. The case when the cliques have pairwise intersections of size at most one seems particularly challenging. Here, we give lower bounds by analyzing a random greedy hypergraph process. We also consider the related question of determining the maximum number of caps in a finite projective/affine plane and obtain nontrivial upper and lower bounds. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is a dynamic imaging technique that uses high‐frequency sound waves to capture live images of the structures beneath the skin. In addition to its growing use in diagnosis and interventions, ultrasound imaging has the potential to reinforce concepts in the undergraduate medical curriculum. However, research assessing the impact of ultrasound on anatomy learning and student cognition is scarce. The purpose of this study was to compare the impact of ultrasound‐based instruction versus narrated videos on students' understanding of anatomical relationships, as well as the role of intrinsic motivation, self‐efficacy beliefs, and students' attitudes in this process. A booster course on anterior leg and wrist anatomy was offered to second‐year medical students. A randomized controlled trial with a cross‐over design allocated students to either an ultrasound‐based teaching condition (cohort A) or a narrated anatomy video condition (cohort B). Next, participants were crossed to the alternative intervention. At the start of the study (T0), baseline anatomy knowledge, intrinsic motivation, self‐efficacy beliefs, and spatial ability were measured. After the first intervention (T1) and at the end of the study (T2), both cohorts were administered an anatomy test, an intrinsic motivation scale, and a self‐efficacy scale. In addition, each student was asked to fill out a perception survey after the ultrasound intervention. Finally, building on the cross‐over design, the most optimal sequence of interventions was examined. A total of 181 students participated (cohort A: n = 82, cohort B: n = 99). Both cohorts performed comparably on the baseline anatomy knowledge test, spatial ability test, intrinsic motivation, and self‐efficacy scale. At T1, cohort B outperformed cohort A on the anatomy test (p = 0.019), although only a small effect size could be detected (Cohen's d = 0.34). Intrinsic motivation and self‐efficacy of both cohorts were similar at T1. At T2, the anatomy test, intrinsic motivation, and self‐efficacy scale did not reflect an effect after studying either sequence of the interventions. Students reported favorably about the ultrasound experience, but also mentioned a steep learning curve. Medical students found the hands‐on ultrasound sessions to be valuable, increasing their interest in musculoskeletal anatomy and ultrasound imaging. However, the addition of ultrasound did not result in superior spatial anatomy understanding compared to watching anatomy videos. In addition, ultrasound teaching did not have a major effect on student cognition. Ultrasound‐based teaching of musculoskeletal anatomy is regarded as difficult to learn, and therefore it is hypothesized that too high levels of cognitive load might explain the presented results. [ABSTRACT FROM AUTHOR]

The Pareto principle, or 20:80 rule, describes resource distribution in stable communities whereby 20% of community members acquire 80% of a key resource. In this Burning Question, we ask to what extent the Pareto principle applies to the acquisition of limiting resources in stable microbial communities; how it may contribute to our understanding of microbial interactions, microbial community exploration of evolutionary space, and microbial community dysbiosis; and whether it can serve as a benchmark of microbial community stability and functional optimality? [ABSTRACT FROM AUTHOR]

There is much human disadvantage and unmet need in the world, including deficits in basic resources and services considered to be human rights, such as drinking water, sanitation and hygiene, healthy nutrition, access to basic healthcare, and a clean environment. Furthermore, there are substantive asymmetries in the distribution of key resources among peoples. These deficits and asymmetries can lead to local and regional crises among peoples competing for limited resources, which, in turn, can become sources of discontent and conflict. Such conflicts have the potential to escalate into regional wars and even lead to global instability. Ergo: in addition to moral and ethical imperatives to level up, to ensure that all peoples have basic resources and services essential for healthy living and to reduce inequalities, all nations have a self‐interest to pursue with determination all available avenues to promote peace through reducing sources of conflicts in the world. Microorganisms and pertinent microbial technologies have unique and exceptional abilities to provide, or contribute to the provision of, basic resources and services that are lacking in many parts of the world, and thereby address key deficits that might constitute sources of conflict. However, the deployment of such technologies to this end is seriously underexploited. Here, we highlight some of the key available and emerging technologies that demand greater consideration and exploitation in endeavours to eliminate unnecessary deprivations, enable healthy lives of all and remove preventable grounds for competition over limited resources that can escalate into conflicts in the world. We exhort central actors: microbiologists, funding agencies and philanthropic organisations, politicians worldwide and international governmental and non‐governmental organisations, to engage – in full partnership – with all relevant stakeholders, to 'weaponise' microbes and microbial technologies to fight resource deficits and asymmetries, in particular among the most vulnerable populations, and thereby create humanitarian conditions more conducive to harmony and peace. [ABSTRACT FROM AUTHOR]

Background: Dietary supplementation with branched‐chain amino acids (BCAA) is often used in cirrhotic patients to improve nutritional status. We wanted to explore the evidence for BCAA supplementation in chronic liver disease. Methods: We searched MEDLINE and EMBASE for studies with BCAA supplementation with the presence of a disease‐control group (placebo or no intervention) using search terms 'liver cirrhosis', 'hepatocellular carcinoma', 'branched chain amino acids' and relevant synonyms. Risk of bias was assessed using ROBINS‐I and RoB 2.0 tools. Meta‐analyses were performed with a random‐effects model. Results were reported following EQUATOR guidelines. Results: Of 3378 studies screened by title and abstract, 54 were included (34 randomized controlled trials, 5 prospective case–control studies, 13 retrospective case–control studies: in total 2308 patients BCAA supplementation, 2876 disease‐controls). Risk of bias was high/serious for almost all studies. According to meta‐analyses, long‐term (at least 6 months) BCAA supplementation in cirrhotic patients significantly improved event‐free survival (p =.008; RR.61 95% CI.42–.88) and tended to improve overall survival (p =.05; RR.58 95% CI.34–1.00). Two retrospective studies suggested the beneficial effects during sorafenib for hepatocellular carcinoma. Available studies reported no beneficial effects or contradictory results of BCAA after other specific therapeutic interventions (resection or radiological interventions for hepatocellular carcinoma, liver transplantation, paracentesis or variceal ligation). No convincing beneficial effects of BCAA supplementation on liver function, nutritional status or quality of life were found. No study reported serious side effects of BCAA. Conclusions: Prophylactic BCAA supplementation appears safe and might improve survival in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Etazene (or etodesnitazene) is a novel and highly active synthetic opioid belonging to the rapidly evolving and emerging group of "nitazenes." Etazene metabolites were identified through analysis of a human urine sample. The sample was obtained from a 25‐year‐old man who attempted suicide by taking a new psychoactive substances (NPS) cocktail purchased online and was analyzed by ultrahigh performance liquid chromatography‐high‐resolution mass spectrometry (UHPLC‐HRMS). Etazene metabolites were predicted with BioTransformer 3.0, and the exact masses were added to the inclusion list. Eight possible metabolites were identified in the urine sample. N‐ and O‐deethylation were identified as the predominant metabolism routes, resulting in M1 (O‐deethylated etazene; most abundant metabolite based on the peak area), M2 (N‐deethylated etazene), and M3 (N,O‐dideethylated etazene) metabolites. Less abundant hydroxylated products of these deethylated metabolites and etazene were also found. Additionally, in the analysis without β‐glucuronidase treatment, M1‐ and M3‐glucuronide phase II metabolites were found. As N‐ and O‐deethylated products seem to be the predominant urinary metabolites, the detection of these metabolites in urine can be useful to demonstrate etazene exposure. [ABSTRACT FROM AUTHOR]

A Monte Carlo approach is used to generate 2D and 3D networks of randomly connected cylindrical pores with a variety of configurations. These networks are created to represent the gamma‐alumina supports of hydrotreating catalysts. Textural properties from generated pore networks are compared with experimental values of porosity, specific surface area, and specific pore volume. The experimental properties were estimated using a helium pycnometer and nitrogen sorption isotherms for five gamma‐alumina samples. Simulated and experimental textural properties concur. Internal diffusion is simulated by 1D Fick diffusion within each pore of the network. A macroscopic diffusion parameter for vacuum distillate type molecules, previously obtained by inverse liquid chromatography and by pulsed‐field gradient nuclear magnetic resonance experiments on alumina samples, is predicted and confronted with experimental values. Diffusional properties are in good agreement when considering two hierarchically organized porous domains. [ABSTRACT FROM AUTHOR]

Nitrogen is the most crucial element in the production of nutritious feeds and foods. The production of reactive nitrogen by means of fossil fuel has thus far been able to guarantee the protein supply for the world population. Yet, the production and massive use of fertilizer nitrogen constitute a major threat in terms of environmental health and sustainability. It is crucial to promote consumer acceptance and awareness towards proteins produced by highly effective microorganisms, and their potential to replace proteins obtained with poor nitrogen efficiencies from plants and animals. The fact that reactive fertilizer nitrogen, produced by the Haber Bosch process, consumes a significant amount of fossil fuel worldwide is of concern. Moreover, recently, the prices of fossil fuels have increased the cost of reactive nitrogen by a factor of 3 to 5 times, while international policies are fostering the transition towards a more sustainable agro‐ecology by reducing mineral fertilizers inputs and increasing organic farming. The combination of these pressures and challenges opens opportunities to use the reactive nitrogen nutrient more carefully. Time has come to effectively recover used nitrogen from secondary resources and to upgrade it to a legal status of fertilizer. Organic nitrogen is a slow‐release fertilizer, it has a factor of 2.5 or higher economic value per unit nitrogen as fertilizer and thus adequate technologies to produce it, for instance by implementing photobiological processes, are promising. Finally, it appears wise to start the integration in our overall feed and food supply chains of the exceptional potential of biological nitrogen fixation. Nitrogen produced by the nitrogenase enzyme, either in the soil or in novel biotechnology reactor systems, deserves to have a 'renaissance' in the context of planetary governance in general and the increasing number of people who desire to be fed in a sustainable way in particular. [ABSTRACT FROM AUTHOR]

(F) FACS-sorted CD4+CD25+CD127-Tregs, cultured in vitro for 6-7 days, were nucleofected with 100nM control siRNA (CTRL) or siRNA targeted to Gal10 (Gal10 siRNA). Gal10 mRNA expression studied using Taqman probe Hs00171342 m16 and normalized according to B2 M mRNA expression (left graph), or using Gal10 primers previously described by Kubach et al.5 and normalized according to B2M (middle graph) or EF1A (right graph) mRNA expression. The Charcot-Leyden crystal protein galectin-10 is not a major determinant of human regulatory T-cell function. [Extracted from the article]

In stochastic (dynamic) traffic assignment (DTA), route choice (RC) formulations with implicit route set require less memory than their explicit counterparts. To compute turn probabilities, however, a topological ordering of the nodes is needed, which negatively impacts the stability of convergence and consistency of equilibrium. This paper formulates a general framework for the RC module of the efficient stochastic DTA (ESDTA) without topological ordering; we demonstrate how its full fixed route yields smooth and consistent convergence. The theoretical framework requires a series of computational modifications to ensure that numerical errors remain limited and to make the formulation more efficient for use in practice. The resulting ESDTA's computation time to reach equilibrium scales linearly with respect to all relevant complexity dimensions (network size, demand zones, time resolution, and congestion level). [ABSTRACT FROM AUTHOR]

Summary: Thiamin (or thiamine), known as vitamin B1, represents an indispensable component of human diets, being pivotal in energy metabolism. Thiamin research depends on adequate vitamin quantification in plant tissues. A recently developed quantitative liquid chromatography–tandem mass spectrometry (LC–MS/MS) method is able to assess the level of thiamin, its phosphorylated entities and its biosynthetic intermediates in the model plant Arabidopsis thaliana, as well as in rice. However, their implementation requires expensive equipment and substantial technical expertise. Microbiological assays can be useful in deter‐mining metabolite levels in plant material and provide an affordable alternative to MS‐based analysis.Here, we evaluate, by comparison to the LC–MS/MS reference method, the potential of a carefully chosen panel of yeast assays to estimate levels of total vitamin B1, as well as its biosynthetic intermediates pyrimidine and thiazole in Arabidopsis samples.The examined panel of Saccharomyces cerevisiae mutants was, when implemented in microbiological assays, capable of correctly assigning a series of wild‐type and thiamin biofortified Arabidopsis plant samples.The assays provide a readily applicable method allowing rapid screening of vitamin B1 (and its biosynthetic intermediates) content in plant material, which is particularly useful in metabolic engineering approaches and in germplasm screening across or within species. [ABSTRACT FROM AUTHOR]

The planet is experiencing all manner of environmental crises, and crises that have their origins in the environment, including global warming, pollution of the air, soil, marine systems and freshwater, loss of habitats and species extinctions, transmission of deadly animal infections to humans, the spread of antimicrobial resistance, to name just a few. Planetary boundaries are being successively breached. Devising and implementing optimal solution and mitigation strategies urgently requires the best possible scientific brains to be harnessed and focused on environmental crises. It is imperative to establish authoritative leadership and the intellectual and organisational framework for this: a European Environmental Research Organisation, modelled on the European Molecular Biology Organisation (EMBO) and Laboratory (EMBL), whose mission is to carry out pioneering research on environmental crisis‐relevant topics, communicate its findings and recommendations to governments, their agencies, the general public, business and other stakeholders, and create outstanding research leaders to populate the best institutions worldwide – a global network of top scientists working together to understand the causes and nature of crises and to devise effective solutions. [ABSTRACT FROM AUTHOR]

The core responsibility of governments is the security of their citizens, and this means inter alia protecting their safety, nutrition and health. Microbiology and microbial biotechnology have key roles to play in improving supply security of essential resources. In this paper, we discuss the urgent need to fully and immediately exploit existing microbial biotechnologies to maximize supply security of energy, food and medical supplies, and of waste management, and to invest in new research specifically targetting supply security of essential resources. [ABSTRACT FROM AUTHOR]

Summary: The transition to sustainable agriculture and horticulture is a societal challenge of global importance. Fertilization with a minimum impact on the environment can facilitate this. Organic fertilizers can play an important role, given their typical release pattern and production through resource recovery. Microbial fertilizers (MFs) constitute an emerging class of organic fertilizers and consist of dried microbial biomass, for instance produced on effluents from the food and beverage industry. In this study, three groups of organisms were tested as MFs: a high‐rate consortium aerobic bacteria (CAB), the microalga Arthrospira platensis ('Spirulina') and a purple non‐sulfur bacterium (PNSB) Rhodobacter sp. During storage as dry products, the MFs showed light hygroscopic activity, but the mineral and organic fractions remained stable over a storage period of 91 days. For biological tests, a reference organic fertilizer (ROF) was used as positive control, and a commercial organic growing medium (GM) as substrate. The mineralization patterns without and with plants were similar for all MFs and ROF, with more than 70% of the organic nitrogen mineralized in 77 days. In a first fertilization trial with parsley, all MFs showed equal performance compared to ROF, and the plant fresh weight was even higher with CAB fertilization. CAB was subsequently used in a follow‐up trial with petunia and resulted in elevated plant height, comparable chlorophyll content and a higher amount of flowers compared to ROF. Finally, a cost estimation for packed GM with supplemented fertilizer indicated that CAB and a blend of CAB/PNSB (85%/15%) were most cost competitive, with an increase of 6% and 7% in cost compared to ROF. In conclusion, as bio‐based fertilizers, MFs have the potential to contribute to sustainable plant nutrition, performing as good as a commercially available organic fertilizer, and to a circular economy. [ABSTRACT FROM AUTHOR]

Mammalian cells are commonly used to produce recombinant protein therapeutics, but suffer from a high cost per mg of protein produced. There is therefore great interest in improving protein yields to reduce production cost. We present an entirely novel approach to reach this goal through direct engineering of the cellular translation machinery by introducing the R98S point mutation in the catalytically essential ribosomal protein L10 (RPL10‐R98S). Our data support that RPL10‐R98S enhances translation levels and fidelity and reduces proteasomal activity in lymphoid Ba/F3 and Jurkat cell models. In HEK293T cells cultured in chemically defined medium, knock‐in of RPL10‐R98S was associated with a 1.7‐ to 2.5‐fold increased production of four transiently expressed recombinant proteins and 1.7‐fold for one out of two stably expressed proteins. In CHO‐S cells, eGFP reached a 2‐fold increased expression under stable but not transient conditions, but there was no production benefit for monoclonal antibodies. The RPL10‐R98S associated production gain thus depends on culture conditions, cell type, and the nature of the expressed protein. Our study demonstrates the potential for using a ribosomal protein mutation for pharmaceutical protein production gains, and further research on how various factors influence RPL10‐R98S phenotypes can maximize its exploitability for the mammalian protein production industry. [ABSTRACT FROM AUTHOR]

Summary: Microbial technologies have provided solutions to key challenges in our daily lives for over a century. In the debate about the ongoing climate change and the need for planetary sustainability, microbial ecology and microbial technologies are rarely considered. Nonetheless, they can bring forward vital solutions to decrease and even prevent long‐term effects of climate change. The key to the success of microbial technologies is an effective, target‐oriented microbiome management. Here, we highlight how microbial technologies can play a key role in both natural, i.e. soils and aquatic ecosystems, and semi‐natural or even entirely human‐made, engineered ecosystems, e.g. (waste) water treatment and bodily systems. First, we set forward fundamental guidelines for effective soil microbial resource management, especially with respect to nutrient loss and greenhouse gas abatement. Next, we focus on closing the water circle, integrating resource recovery. We also address the essential interaction of the human and animal host with their respective microbiomes. Finally, we set forward some key future potentials, such as microbial protein and the need to overcome microphobia for microbial products and services. Overall, we conclude that by relying on the wisdom of the past, we can tackle the challenges of our current era through microbial technologies. [ABSTRACT FROM AUTHOR]

Summary: Clostridia comprise bacteria of environmental, biotechnological and medical interest and many commensals of the gut microbiota. Because of their strictly anaerobic lifestyle, oxygen is a major stress for Clostridia. However, recent data showed that these bacteria can cope with O2 better than expected for obligate anaerobes through their ability to scavenge, detoxify and consume O2. Upon O2 exposure, Clostridia redirect their central metabolism onto pathways less O2‐sensitive and induce the expression of genes encoding enzymes involved in O2‐reduction and in the repair of oxidized damaged molecules. While Faecalibacterium prausnitzii efficiently consumes O2 through a specific extracellular electron shuttling system requiring riboflavin, enzymes such as rubrerythrins and flavodiiron proteins with NAD(P)H‐dependent O2‐ and/or H2O2‐reductase activities are usually encoded in other Clostridia. These two classes of enzymes play indeed a pivotal role in O2 tolerance in Clostridioides difficile and Clostridium acetobutylicum. Two main signalling pathways triggering O2‐induced responses have been described so far in Clostridia. PerR acts as a key regulator of the O2‐ and/or reactive oxygen species–defence machinery while in C. difficile, σB, the sigma factor of the general stress response also plays a crucial role in O2 tolerance by controlling the expression of genes involved in O2 scavenging and repair systems. [ABSTRACT FROM AUTHOR]

An ultra‐high pressure liquid chromatography high‐resolution mass spectrometric (UHPLC–HRMS) method was developed for the simultaneous and sensitive quantification of 10 β‐lactam antibiotics (cefepime, meropenem, amoxicillin, cefazolin, benzylpenicillin, ceftazidime, piperacillin, flucloxacillin, cefuroxime and aztreonam), linezolid and β‐lactamase inhibitors tazobactam and clavulanic acid in human plasma. Validation according to the EMA guidelines showed excellent within‐ and between‐run accuracy and precision (i.e. between 1.1 and 8.5%) and high sensitivity (i.e. lower limit of quantification between 0.25 and 1 mg/L). The UHPLC–HRMS method enables a short turnaround time and high sensitivity and needs only a small amount of plasma, allowing appropriate routine therapeutic drug monitoring. The short turnaround time is obtained by speeding up the protocol on multiple levels, i.e. fast and workload‐efficient sample preparation (i.e. protein precipitation and dilution), short (4 min) instrument run time, simultaneous measurement of all relevant β‐lactam antibiotics used in the intensive care unit and the use of the same instrument, column and mobile phases as for the other routine methods in our laboratory. [ABSTRACT FROM AUTHOR]

Summary: Rice is a major food crop to approximately half of the human population. Unfortunately, the starchy endosperm, which is the remaining portion of the seed after polishing, contains limited amounts of micronutrients. Here, it is shown that this is particularly the case for thiamin (vitamin B1). Therefore, a tissue‐specific metabolic engineering approach was conducted, aimed at enhancing the level of thiamin specifically in the endosperm. To achieve this, three major thiamin biosynthesis genes, THIC, THI1 and TH1, controlled by strong endosperm‐specific promoters, were employed to obtain engineered rice lines. The metabolic engineering approaches included ectopic expression of THIC alone, in combination with THI1 (bigenic) or combined with both THI1 and TH1 (trigenic). Determination of thiamin and thiamin biosynthesis intermediates reveals the impact of the engineering approaches on endosperm thiamin biosynthesis. The results show an increase of thiamin in polished rice up to threefold compared to WT, and stable upon cooking. These findings confirm the potential of metabolic engineering to enhance de novo thiamin biosynthesis in rice endosperm tissue and aid in steering future biofortification endeavours. [ABSTRACT FROM AUTHOR]

Summary: Anaerobic digesters produce biogas, a mixture of predominantly CH4 and CO2, which is typically incinerated to recover electrical and/or thermal energy. In a context of circular economy, the CH4 and CO2 could be used as chemical feedstock in combination with ammonium from the digestate. Their combination into protein‐rich bacterial, used as animal feed additive, could contribute to the ever growing global demand for nutritive protein sources and improve the overall nitrogen efficiency of the current agro‐ feed/food chain. In this concept, renewable CH4 and H2 can serve as carbon‐neutral energy sources for the production of protein‐rich cellular biomass, while assimilating and upgrading recovered ammonia from the digestate. This study evaluated the potential of producing sustainable high‐quality protein additives in a decentralized way through coupling anaerobic digestion and microbial protein production using methanotrophic and hydrogenotrophic bacteria in an on‐farm bioreactor. We show that a practical case digester handling liquid piggery manure, of which the energy content is supplemented for 30% with co‐substrates, provides sufficient biogas to allow the subsequent microbial protein as feed production for about 37% of the number of pigs from which the manure was derived. Overall, producing microbial protein on the farm from available methane and ammonia liberated by anaerobic digesters treating manure appears economically and technically feasible within the current range of market prices existing for high‐quality protein. The case of producing biomethane for grid injection and upgrading the CO2 with electrolytic hydrogen to microbial protein by means of hydrogen‐oxidizing bacteria was also examined but found less attractive at the current production prices of renewable hydrogen. Our calculations show that this route is only of commercial interest if the protein value equals the value of high‐value protein additives like fishmeal and if the avoided costs for nutrient removal from the digestate are taken into consideration. [ABSTRACT FROM AUTHOR]

Even the best quality 2D materials have non‐negligible concentrations of vacancies and impurities. It is critical to understand and quantify how defects change intrinsic properties, and use this knowledge to generate functionality. This challenge can be addressed by employing many‐body perturbation theory to obtain the optical absorption spectra of defected transition metal dichalcogenides. Herein metal vacancies, which are largely unreported, show a larger set of polarized excitons than chalcogenide vacancies, introducing localized excitons in the sub‐optical‐gap region, whose wave functions and spectra make them good candidates as quantum emitters. Despite the strong interaction with substitutional defects, the spin texture and pristine exciton energies are preserved, enabling grafting and patterning in optical detectors, as the full optical‐gap region remains available. A redistribution of excitonic weight between the A and B excitons is visible in both cases and may allow the quantification of the defect concentration. This work establishes excitonic signatures to characterize defects in 2D materials and highlights vacancies as qubit candidates for quantum computing. [ABSTRACT FROM AUTHOR]

Summary: Objective: One third of epilepsy patients do not become seizure‐free using conventional medication. Therefore, there is a need for alternative treatments. Preclinical research using designer receptors exclusively activated by designer drugs (DREADDs) has demonstrated initial success in suppressing epileptic activity. Here, we evaluated whether long‐term chemogenetic seizure suppression could be obtained in the intraperitoneal kainic acid rat model of temporal lobe epilepsy, when DREADDs were selectively expressed in excitatory hippocampal neurons. Methods: Epileptic male Sprague Dawley rats received unilateral hippocampal injections of adeno‐associated viral vector encoding the inhibitory DREADD hM4D(Gi), preceded by a cell‐specific promotor targeting excitatory neurons. The effect of clozapine‐mediated DREADD activation on dentate gyrus evoked potentials and spontaneous electrographic seizures was evaluated. Animals were systemically treated with single (.1 mg/kg/24 h) or repeated (.1 mg/kg/6 h) injections of clozapine. In addition, long‐term continuous release of clozapine and olanzapine (2.8 mg/kg/7 days) using implantable minipumps was evaluated. All treatments were administered during the chronic epileptic phase and between 1.5 and 13.5 months after viral transduction. Results: In the DREADD group, dentate gyrus evoked potentials were inhibited after clozapine treatment. Only in DREADD‐expressing animals, clozapine reduced seizure frequency during the first 6 h postinjection. When administered repeatedly, seizures were suppressed during the entire day. Long‐term treatment with clozapine and olanzapine both resulted in significant seizure‐suppressing effects for multiple days. Histological analysis revealed DREADD expression in both hippocampi and some cortical regions. However, lesions were also detected at the site of vector injection. Significance: This study shows that inhibition of the hippocampus using chemogenetics results in potent seizure‐suppressing effects in the intraperitoneal kainic acid rat model, even 1 year after viral transduction. Despite a need for further optimization, chemogenetic neuromodulation represents a promising treatment prospect for temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Cancer cells hijack metabolic pathways in order to provide themselves with building blocks to support their proliferation and survival. Upregulation and addiction to de novo serine/glycine synthesis is an example of metabolic rewiring in cancer cells whereby serine and glycine are synthesised via a side branch of glycolysis. In this review, we focus on upregulation of endogenous serine/glycine production in acute leukemia, namely T‐cell acute leukemia (T‐ALL) and acute myeloid leukemia (AML). Several genetic lesions directly driving the serine/glycine addiction in acute leukemia have been established. Additionally, indirect regulation of de novo serine/glycine synthesis is observed in acute leukemia. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of small monodisperse multimodal iron oxide nanoparticles (IONPs), functionalized with boron‐dipyrromethene (BODIPY) derivatives is described. Optical and relaxometric properties of the nanoparticles have been evaluated, suggesting a potential applicability of the particles as bimodal contrast agent for magnetic resonance and optical imaging. The BODIPY funcionalized IONPs showed bright fluorescence and high transverse relaxivity r2 which was in the range 47‐49 mM−1 s−1. Two‐photon fluorescence microscopy experiments performed at 1100 nm revealed that BODIPY‐functionalized IONPs showed significant increase in two‐photon fluorescence compared to the bare nanoparticles, suggesting their potential for applications in multimodal imaging. Cell viability studies on rat tumor (AR42J) and human ovarian cancer (SKOV3) cells showed no significant cytotoxicity at any of the tested concentrations, while greater sensitivity was observed for human hepatic stellate (GRX), human umbilical vein (HUVEC) and rat insulinoma (INS1) cells at higher nanoparticle concentrations. [ABSTRACT FROM AUTHOR]

Background: Deep venous thrombosis (DVT) is a common postoperative complication in patients undergoing major orthopaedic surgery of the lower limbs, such as total hip or knee replacement (THR, TKR). Routine pharmacological thromboprophylaxis with low‐molecular‐weight heparin (LMWH) or a direct oral anticoagulant agent is strongly recommended in this setting. THR and TKR as well as ankle arthrodesis are frequently performed in people with haemophilia (PWH) and chronic haemophilic arthropathy. Pharmacological thromboprophylaxis in this population remains controversial. Methods: We report the results of a single‐centre prospective study initiated in 2002 evaluating by systematic Doppler ultrasound the incidence of subclinical DVT in consecutive PWH referred for major orthopaedic surgery and not receiving pharmacological thromboprophylaxis. Results: We included 46 different PWH (39 Haemophilia A, 7 Haemophilia B, 27 severe, 15 moderate and 4 mild forms) undergoing 67 orthopaedic procedures. Most (89.5%) were performed with continuous infusion of clotting factor concentrates. Rehabilitation was usually started on day 1 post‐op. No clinical DVT or pulmonary embolism was suspected. In total, there were 5 cases (3 severe, 1 moderate HA and 1 moderate HB) of subclinical DVT which were all distal. Two patients were treated with a short course (10‐14 days) of LMWH. The overall incidence of DVT was 7.5%. Conclusions: These data provide imaging‐based evidence that the risk of DVT following major orthopaedic surgery among PWH is low. Identified DVTs were distal and resolved spontaneously in most cases. Systematic pharmacological thromboprophylaxis in this specific population is probably for most patients not required. [ABSTRACT FROM AUTHOR]

Objective: Pathogenic variants in SCN3A, encoding the voltage-gated sodium channel subunit Nav1.3, cause severe childhood onset epilepsy and malformation of cortical development. Here, we define the spectrum of clinical, genetic, and neuroimaging features of SCN3A-related neurodevelopmental disorder.Methods: Patients were ascertained via an international collaborative network. We compared sodium channels containing wild-type versus variant Nav1.3 subunits coexpressed with β1 and β2 subunits using whole-cell voltage clamp electrophysiological recordings in a heterologous mammalian system (HEK-293T cells).Results: Of 22 patients with pathogenic SCN3A variants, most had treatment-resistant epilepsy beginning in the first year of life (16/21, 76%; median onset, 2 weeks), with severe or profound developmental delay (15/20, 75%). Many, but not all (15/19, 79%), exhibited malformations of cortical development. Pathogenic variants clustered in transmembrane segments 4 to 6 of domains II to IV. Most pathogenic missense variants tested (10/11, 91%) displayed gain of channel function, with increased persistent current and/or a leftward shift in the voltage dependence of activation, and all variants associated with malformation of cortical development exhibited gain of channel function. One variant (p.Ile1468Arg) exhibited mixed effects, with gain and partial loss of function. Two variants demonstrated loss of channel function.Interpretation: Our study defines SCN3A-related neurodevelopmental disorder along a spectrum of severity, but typically including epilepsy and severe or profound developmental delay/intellectual disability. Malformations of cortical development are a characteristic feature of this unusual channelopathy syndrome, present in >75% of affected individuals. Gain of function at the channel level in developing neurons is likely an important mechanism of disease pathogenesis. ANN NEUROL 2020;88:348-362. [ABSTRACT FROM AUTHOR]

Summary: Pure (single) cultures of microorganisms and mixed microbial communities (microbiomes) have been important for centuries in providing renewable energy, clean water and food products to human society and will continue to play a crucial role to pursue the Sustainable Development Goals. To use microorganisms effectively, microbial engineered processes require adequate control. Microbial communities are shaped by manageable deterministic processes, but also by stochastic processes, which can promote unforeseeable variations and adaptations. Here, we highlight the impact of stochasticity in single culture and microbiome engineering. First, we discuss the concepts and mechanisms of stochasticity in relation to microbial ecology of single cultures and microbiomes. Second, we discuss the consequences of stochasticity in relation to process performance and human health, which are reflected in key disadvantages and important opportunities. Third, we propose a suitable decision tool to deal with stochasticity in which monitoring of stochasticity and setting the boundaries of stochasticity by regulators are central aspects. Stochasticity may give rise to some risks, such as the presence of pathogens in microbiomes. We argue here that by taking the necessary precautions and through clever monitoring and interpretation, these risks can be mitigated. [ABSTRACT FROM AUTHOR]

Fault diagnosis can help extend the lifetime of fuel cells and has been widely explored for externally humidified fuel cells. However, fault detection in self‐humidified fuel cells is scarce, despite its importance. This paper explores various wavelet‐based descriptors for identifying hydration levels in self‐humidified stacks. Wavelet‐based techniques are non‐intrusive and provide concurrent examinations in time and frequency. Thus, they encapsulate health related data that can be used as health monitoring features. The specific wavelet‐based techniques used here are (i) impedance obtained through the wavelet‐based fast electrochemical impedance spectroscopy (EIS) and (ii) changes in wavelet energy through wavelet and wavelet packet decomposition. Results are compared based on their trends under dehydration conditions and the robustness of those trends across different currents and sampling rates. They are then assessed based on their predictive ability using RReliefF (Regression‐ReliefF)‐ a regression based feature ranking tool. Based on the qualitative and quantitative analysis, descriptors are assessed in the context of creating a short‐term health monitoring system for self‐humidified fuel cells. While a modified version of the wavelet energies provides the best results for differentiating faults, fast EIS opens the possibility for analysis of more complex fault modes and is shown to be more robust. [ABSTRACT FROM AUTHOR]

Background: MRI of the clavicle's sternal end has been studied for age estimation. Several pitfalls have been noted, but how they affect age estimation performance remains unclear. Purpose/Hypothesis: To further study these pitfalls and to make suggestions for a proper use of clavicle MRI for forensic age estimation. Our hypotheses were that age estimation would benefit from 1) discarding stages 1 and 4/5; 2) including advanced substages 3aa, 3ab, and 3ac; 3) taking both clavicles into account; and 4) excluding morphological variants. Study Type: Prospective cross‐sectional. Population: Healthy Caucasian volunteers between 11 and 30 years old (524; 277 females, 247 males). Field Strength/Sequence: 3T, T1‐weighted gradient echo volumetric interpolated breath‐hold examination (VIBE) MR‐sequence. Assessment: Four observers applied the most elaborate staging technique for long bone development that has been described in the current literature (including stages, substages, and advanced substages). One of the observers repeated a random selection of the assessments in 110 participants after a 2‐week interval. Furthermore, all observers documented morphological variants. Statistical Tests: Weighted kappa quantified reproducibility of staging. Bayes' rule was applied for age estimation with a continuation ratio model for the distribution of the stages. According to the hypotheses, different models were tested. Mean absolute error (MAE) differences between models were compared, as were MAEs between cases with and without morphological variants. Results: Weighted kappa equaled 0.82 for intraobserver and ranged between 0.60 and 0.64 for interobserver agreement. Stages 1 and 4/5 were allocated interchangeably in 4.3% (54/1258). Age increased steadily in advanced substages of stage 3, but improvement in age estimation was not significant (right P = 0.596; left P = 0.313). The model that included both clavicles and discarded stages 1 and 4/5 yielded an MAE of 1.97 years, a root mean squared error of 2.60 years, and 69% correctly classified minors. Morphological variants rendered significantly higher MAEs (right 3.84 years, P = 0.015; left 2.93 years, P = 0.022). Data Conclusion: Our results confirmed hypotheses 3) and 4), while hypotheses 1) and 2) remain to be investigated in larger studies. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:377–388. [ABSTRACT FROM AUTHOR]

Innovative monocyclic β‐lactam entities create opportunities in the battle against resistant bacteria because of their PBP acylation potential, intrinsically high β‐lactamase stability and compact scaffold. α‐Benzylidene‐substituted 3‐amino‐1‐carboxymethyl‐β‐lactams were recently shown to be potent PBP inhibitors and constitute eligible anchor points for synthetic elaboration of the chemical space around the central β‐lactam ring. The present study discloses a 12‐step synthesis of ten α‐arylmethylidenecarboxylates using a microwave‐assisted Wittig olefination as the crucial reaction step. The library was designed aiming at enhanced β‐lactam electrophilicity and extended electron flow after enzymatic attack. Additionally, increased β‐lactamase stability and intermolecular target interaction were envisioned by tackling both the substitution pattern of the aromatic ring and the β‐lactam C4‐position. The significance of α‐unsaturation was validated and the R39/PBP3 inhibitory potency shown to be augmented the most through decoration of the aromatic ring with electron‐withdrawing groups. Furthermore, ring cleavage by representative β‐lactamases was ruled out, providing new insights in the SAR landscape of monocyclic β‐lactams as eligible PBP or β‐lactamase inhibitors. [ABSTRACT FROM AUTHOR]

The first steps towards top‐down morphology control in micellar self‐assembly are introduced. Kinetically stable micelles are formed from block copolymers (BCPs) using continuous flow techniques by turbulent mixing of water with a THF solution of polymers. In this way, particle shape and size can be altered from spheres to ellipsoids solely via tuning of mixing parameters from a single BCP. [ABSTRACT FROM AUTHOR]

Summary: Clostridium difficile is the main cause of antibiotic‐associated diarrhoea. Inside the gut, C. difficile must adapt to the stresses it copes with, by inducing protection, detoxification and repair systems that belong to the general stress response involving σB. Following stresses, σB activation requires a PP2C phosphatase to dephosphorylate the anti‐anti‐sigma factor RsbV that allows its interaction with the anti‐sigma factor RsbW and the release of σB. In this work, we studied the signalling pathway responsible for the activation of σB in C. difficile. Contrary to other firmicutes, the expression of sigB in C. difficile is constitutive and not autoregulated. We confirmed the partner switching mechanism that involved RsbV, RsbW and σB. We also showed that CD2685, renamed RsbZ, and its phosphatase activity are required for RsbV dephosphorylation triggering σB activation. While CD0007 and CD0008, whose genes belong to the sigB operon, are not involved in σB activity, depletion of the essential iron–sulphur flavoprotein, CD2684, whose gene forms an operon with rsbZ, prevents σB activation. Finally, we observed that σB is heterogeneously active in a subpopulation of C. difficile cells from the exponential phase, likely leading to a 'bet‐hedging' strategy allowing a better chance for the cells to survive adverse conditions. [ABSTRACT FROM AUTHOR]