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BACKGROUND: A traditional view is that stem cells (SCs) divide slowly. Meanwhile, both embryonic and pluripotent SCs display a shorter cell cycle duration (CCD) in comparison to more committed progenitors (CPs). METHODS: We examined the in vitro proliferation and cycling behavior of somatic adult human cells using live cell imaging of passage zero keratinocytes and single-cell RNA sequencing. RESULTS: We found two populations of keratinocytes: those with short CCD and protracted near exponential growth, and those with long CCD and terminal differentiation. Applying the ergodic principle, the comparative numbers of cycling cells in S phase in an enriched population of SCs confirmed a shorter CCD than CPs. Further, analysis of single-cell RNA sequencing of cycling adult human keratinocyte SCs and CPs indicated a shortening of both G1 and G2M phases in the SC. CONCLUSIONS: Contrary to the pervasive paradigm, SCs progress through cell cycle more quickly than more differentiated dividing CPs. Thus, somatic human adult keratinocyte SCs may divide infrequently, but divide rapidly when they divide. Additionally, it was found that SC-like proliferation persisted in vitro.

Abstract The nasal microbiota is a key contributor to animal health, and characterizing the nasal microbiota composition is an important step towards elucidating the role of its different members. Efforts to characterize the nasal microbiota composition of domestic pigs and other farm animals frequently report the presence of bacteria that are typically found in the gut, including many anaerobes from the Bacteroidales and Clostridiales orders. However, the in vivo role of these gut-microbiota associated taxa is currently unclear. Here, we tackled this issue by examining the prevalence, origin, and activity of these taxa in the nasal microbiota of piglets. First, analysis of the nasal microbiota of farm piglets sampled in this study, as well as various publicly available data sets, revealed that gut-microbiota associated taxa indeed constitute a substantial fraction of the pig nasal microbiota that is highly variable across individual animals. Second, comparison of herd-matched nasal and rectal samples at amplicon sequencing variant (ASV) level showed that these taxa are largely shared in the nasal and rectal microbiota, suggesting a common origin driven presumably by the transfer of fecal matter. Third, surgical sampling of the inner nasal tract showed that gut-microbiota associated taxa are found throughout the nasal cavity, indicating that these taxa do not stem from contaminations introduced during sampling with conventional nasal swabs. Finally, analysis of cDNA from the 16S rRNA gene in these nasal samples indicated that gut-microbiota associated taxa are indeed active in the pig nasal cavity. This study shows that gut-microbiota associated taxa are not only present, but also active, in the nasal cavity of domestic pigs, and paves the way for future efforts to elucidate the function of these taxa within the nasal microbiota.

Abstract Background A traditional view is that stem cells (SCs) divide slowly. Meanwhile, both embryonic and pluripotent SCs display a shorter cell cycle duration (CCD) in comparison to more committed progenitors (CPs). Methods We examined the in vitro proliferation and cycling behavior of somatic adult human cells using live cell imaging of passage zero keratinocytes and single-cell RNA sequencing. Results We found two populations of keratinocytes: those with short CCD and protracted near exponential growth, and those with long CCD and terminal differentiation. Applying the ergodic principle, the comparative numbers of cycling cells in S phase in an enriched population of SCs confirmed a shorter CCD than CPs. Further, analysis of single-cell RNA sequencing of cycling adult human keratinocyte SCs and CPs indicated a shortening of both G1 and G2M phases in the SC. Conclusions Contrary to the pervasive paradigm, SCs progress through cell cycle more quickly than more differentiated dividing CPs. Thus, somatic human adult keratinocyte SCs may divide infrequently, but divide rapidly when they divide. Additionally, it was found that SC-like proliferation persisted in vitro.

The molecular contamination of an animal facility was investigated during and after an infection with highly pathogenic African swine fever virus (ASFV) among domestic pigs. The investigation evaluated the risk of indirect transmission of the disease and indicated points that may facilitate cleaning and disinfection processes.

Green hydrogen production is expected to play a major role in the context of the shift towards sustainable energy stipulated in the Fit for 55 package. Green hydrogen and its derivatives have the capacity to act as effective energy storage vectors, while fuel cell-powered vehicles will foster net-zero emission mobility. This study evaluates the potential of green hydrogen production in Power-to-Gas (P2G) systems operated in former mining sites where sand and gravel aggregate has been extracted from lakes and rivers under wet conditions (below the water table). The potential of hydrogen production was assessed for the selected administrative unit in Poland, the West Pomerania province. Attention is given to the legal and organisational aspects of operating mining companies to identify the sites suitable for the installation of floating photovoltaic facilities by 2050. The method relies on the use of GIS tools, which utilise geospatial data to identify potential sites for investments. Basing on the geospatial model and considering technical and organisational constraints, the schedule was developed, showing the potential availability of the site over time. Knowing the surface area of the water reservoir, the installed power of the floating photovoltaic plant, and the production capacity of the power generation facility and electrolysers, the capacity of hydrogen production in the P2G system can be evaluated. It appears that by 2050 it should be feasible to produce green fuel in the P2G system to support a fleet of city buses for two of the largest urban agglomerations in the West Pomerania province. Simulations revealed that with a water coverage ratio increase and the planned growth of green hydrogen generation, it should be feasible to produce fuel for net-zero emission urban mobility systems to power 200 buses by 2030, 550 buses by 2040, and 900 buses by 2050 (for the bus models Maxi (40 seats) and Mega (60 seats)). The results of the research can significantly contribute to the development of projects focused on the production of green hydrogen in a decentralised system. The disclosure of potential and available locations over time can be compared with competitive solutions in terms of spatial planning, environmental and societal impact, and the economics of the undertaking.

O Sistema Único de Saúde (SUS) estende-se por todo território nacional, assegurando a acessibilidade aos serviços de saúde para as diversas esferas sociais, promovendo inúmeras ações nos territórios que visam à prevenção, promoção e reabilitação em saúde, além do acesso integral aos cuidados. Nesse sentido, dentre as assistências proporcionadas pelo SUS, há o Programa Saúde na Escola (PSE) que tem por objetivo viabilizar a articulação entre saúde e educação, propiciando vínculo com os alunos e oportunizando aos estudantes maior conhecimento sobre os serviços ofertados pelo SUS. Nessa perspectiva, este estudo teve como objetivo sensibilizar estudantes do 8º ano do ensino fundamental da rede pública de ensino de Joinville/Santa Catarina sobre a importância do SUS, seus direitos e deveres com relação à saúde. Trata-se de um relato de experiência do projeto denominado “SUStentar” desenvolvido pela Liga Acadêmica de Saúde Coletiva do Instituto Federal de Santa Catarina (LASCIF), em uma escola estadual localizada na cidade de Joinville/SC, que atende cerca de 950 estudantes na faixa etária 6 a 18 anos. O projeto “SUStentar” foi organizado em quatro etapas, sendo elas, articulação ensino serviço, planejamento da ação, ação e avaliação. Os resultados do estudo evidenciaram que os estudantes conseguiram obter novos conhecimentos sobre o SUS, bem como seus princípios e redes de acesso, compreendendo seus direitos como usuários do Sistema. Os métodos utilizados durante as realizações das oficinas mostraram-se positivos e proveitosos pelos estudantes, contribuindo para o desenvolvimento de um pensamento mais crítico relacionado à saúde, especificamente ao SUS. Palavras-chave: Participação Social; Promoção da Saúde; Educação em Saúde; Ensino Fundamental SUStentar: Stimulus to social responsibility in the health for students from public schools at Joinville/SC Abstract: The Unified Health System (SUS) extends throughout the national territory, ensuring accessibility to health services for the various social spheres and promoting numerous actions in the territories aimed at the prevention, promotion, and rehabilitation of health and access integral to care. In this sense, among the assistance provided by the SUS, there is the Health at School Program (PSE), which aims to facilitate the articulation between health and education, providing a bond with students and providing students with greater knowledge about the services offered by the SUS. In this perspective, this study aimed to sensitize students in the 8th year of elementary school in public schools in Joinville/Santa Catarina about the importance of the SUS, their rights, and their duties regarding health. The article is an experience report of the project called “SUStentar,” developed by the Academic League of Collective Health of the Federal Institute of Santa Catarina (LASCIF), in a state school located in the city of Joinville/SC that serves about 950 students, in the age group 6 to 18 years. The “SUStentar” project was organized in four stages: teaching-service articulation, action planning, action, and evaluation. The study results showed that the students could obtain new knowledge about the SUS, as well as its principles and access networks, understanding their rights as users of the System. The methods used during the workshops were positive and valuable for the students, contributing to developing more critical thinking related to health, specifically the SUS. Keywords: Social Participation; Health Promotion; Health Education; Elementary School

Microorganisms adjust metabolic activity to cope with diverse environments. While many studies have provided insights into how individual pathways are regulated, the mechanisms that give rise to coordinated metabolic responses are poorly understood. Here, we identify the regulatory mechanisms that coordinate catabolism and anabolism in Escherichia coli. Integrating protein, metabolite, and flux changes in genetically implemented catabolic or anabolic limitations, we show that combined global and local mechanisms coordinate the response to metabolic limitations. To allocate proteomic resources between catabolism and anabolism, E. coli uses a simple global gene regulatory program. Surprisingly, this program is largely implemented by a single transcription factor, Crp, which directly activates the expression of catabolic enzymes and indirectly reduces the expression of anabolic enzymes by passively sequestering cellular resources needed for their synthesis. However, metabolic fluxes are not controlled by this regulatory program alone; instead, fluxes are adjusted mostly through passive changes in the local metabolite concentrations. These mechanisms constitute a simple but effective global regulatory program that coarsely partitions resources between different parts of metabolism while ensuring robust coordination of individual metabolic reactions.

Cancer cells, like microbes, live in complex metabolic environments. Recent evidence suggests that microbial behavior across metabolic environments is well described by simple empirical growth relationships, or growth laws. Do such empirical growth relationships also exist in cancer cells? To test this question, we develop a high-throughput approach to extract quantitative measurements of cancer cell behaviors in systematically altered metabolic environments. Using this approach, we examine relationships between growth and three frequently studied cancer phenotypes: drug-treatment survival, cell migration, and lactate overflow. Drug-treatment survival follows simple linear growth relationships, which differ quantitatively between chemotherapeutics and EGFR inhibition. Cell migration follows a weak grow-and-go growth relationship, with substantial deviation in some environments. Finally, lactate overflow is mostly decoupled from growth rate and is instead determined by the cells' ability to maintain high sugar uptake rates. Altogether, this work provides a quantitative approach for formulating empirical growth laws of cancer.

African swine fever virus (ASFV) is the etiological agent causing African swine fever (ASF), affecting domestic pigs and wild boar, which is currently the biggest animal epidemic in the world and a major threat to the swine sector. At present, some safety concerns about using LAVs against ASFV still exist despite a commercial vaccine licensed in Vietnam. Therefore, the efforts to identify virulence factors and their mechanisms, as well as to generate new vaccine prototypes, are of major interest. In this work, we have identified the MGF505-2R gene product as an inhibitor of the cGAS/STING pathway, specifically through its interaction with STING protein, controlling IFN-β production. In addition, immunization of a recombinant virus lacking this gene, Arm/07-ΔMGF505-2R, resulted in complete attenuation, demonstrating its involvement in ASFV virulence. Finally, immunization with Arm/07-ΔMGF505-2R induced the generation of antibodies and proved to be partially protective against virulent ASFV strains. These results identify MGF505-2R, as well as its mechanism of action, as a gene contributing to understanding the molecular mechanisms of ASFV virulence, which will be of great value in the design of future vaccine prototypes.

A persistent puzzle in cancer biology is how mutations, which neither alter growth signaling pathways nor directly interfere with drug mechanism, can still recur and persist in tumors. One example is the mutation of the DNA demethylase tet methylcytosine dioxygenase 2 (TET2) in acute myeloid leukemias (AMLs) that frequently persists from diagnosis through remission and relapse, but whose fitness advantage in chemotherapy is unclear. Here, we use isogenic human AML cell lines to show that TET2 loss of function alters the dynamics of transitions between differentiated and stem-like states. A conceptual mathematical model and experimental validation suggest that these altered cell-state dynamics can benefit the cell population by slowing population decay during drug treatment and lowering the number of survivor cells needed to re-establish the initial population. These studies shed light on the functional and phenotypic effects of a TET2 mutation in AML and illustrate how a single gene mutation can alter a cells' phenotypic plasticity. A record of this paper's transparent peer review process is included in the Supplemental Information.

Many microorganisms exhibit nutrient preferences, exemplified by the 'hierarchical' consumption of certain carbon substrates. Here, we systematically investigate under which physiological conditions hierarchical substrate utilization occurs and its mechanisms of implementation. We show utilization hierarchy of Escherichia coli to be ordered by the carbon-uptake flux rather than the identity of the substrates. A detailed study of glycerol uptake finds that it is fully suppressed if the uptake flux of another glycolytic substrate exceeds a threshold, which is set to the influx obtained when grown on glycerol alone. Below this threshold, limited glycerol uptake is 'supplemented' such that the total carbon uptake is maintained at the threshold. This behaviour results from total-flux feedback mediated by cAMP-Crp signalling but also requires inhibition by the regulator fructose 1,6-bisphosphate, which senses the upper-glycolytic flux and ensures that glycerol uptake defers to other glycolytic substrates but not to gluconeogenic ones. A quantitative model reproduces all of the observed utilization patterns, including those of key mutants. The proposed mechanism relies on the differential regulation of uptake enzymes and requires a specific operon organization. This organization is found to be conserved across related species for several uptake systems, suggesting the deployment of similar mechanisms for hierarchical substrate utilization by a spectrum of microorganisms.

It has been observed that in some people in the acute phase of ischemic stroke (IS) there is a tendency to shift the body weight towards the side more affected by the disease and a tendency to spontaneous movements of the upper and/or lower limbs (not covered by the neurological syndrome). The purposes of this study were: to define the kind of behavior observed, and to select symptoms which can predict its occurrence. Participants (n = 222) hospitalized due to first-time IS were assigned to three groups. A: 78 patients with no lateralization of the neurological syndrome (lateralization of the neurological syndrome—LoNS); B: 109 patients with LoNS; O+ group: 35 patients, who at the beginning of hospitalization presented, apart from LoNS, characteristic motor symptoms performed by the less affected side. Patients underwent therapy depending on the neurological symptoms. If the patient showed potential symptoms of a new phenomenon, overactivity of the less affected side (OLAS), a trial therapy (focused on this behavior) was used to confirm it. The predictive symptoms, selected among these from the index day, for the occurrence of OLAS in sitting were distinguished: asymmetry in supine posture and simple, repetitive movements of the nonparetic upper extremity.

Output-based standards set a prescribed target to be achieved by a surveillance system, but they leave the selection of surveillance parameters, such as test type and population to be sampled, to the responsible party in the surveillance area. This allows proportionate legislative surveillance specifications to be imposed over a range of unique geographies. This flexibility makes output-based standards useful in the context of zoonotic threat surveillance, particularly where animal pathogens act as risk indicators for human health or where multiple surveillance streams cover human, animal, and food safety sectors. Yet, these systems are also heavily reliant on the appropriate choice of surveillance options to fit the disease context and the constraints of the organization implementing the surveillance system. Here we describe a framework to assist with designing, implementing, and evaluating output-based surveillance systems showing the effectiveness of a diverse range of activities through a case study example. Despite not all activities being relevant to practitioners in every context, this framework aims to provide a useful toolbox to encourage holistic and stakeholder-focused approaches to the establishment and maintenance of productive output-based surveillance systems.