Pub Date : 2024-06-29DOI: 10.1093/pnasnexus/pgae250
Ellen Peters, David M Markowitz, Ariel Nadratowski, Brittany Shoots-Reinhard
Innumeracy (lack of math skills) among non-scientists often leads climate scientists and others to avoid communicating numbers due to concerns that the public will not understand them and may disengage. However, people often report preferring to receive numbers; providing them also can improve decisions. Here, we demonstrated that the presence vs absence of at least one Arabic integer in climate-related social-media posts increased sharing up to 31.7% but, counter to hypothesis, decreased liking of messages 5.2% in two pre-registered observational studies (climate scientists on Twitter, N>8 million Tweets; climate subreddit, N>17,000 posts and comments). We speculated that the decreased liking was due, not to reduced engagement, but to more negative feelings towards climate-related content described with numeric precision. A pre-registered within-participant experiment (N=212) then varied whether climate consequences were described using Arabic integers (e.g., “90%”) or another format (e.g., verbal terms, “almost all”). The presence of Arabic integers about consequences led to more sharing, wanting to find out more, and greater trust and perceptions of an expert messenger; perceived trust and expertise appeared to mediate effects on sharing and wanting to find out more. Arabic integers about consequences again led to more negative feelings about the Tweets as if numbers clarified the dismaying magnitude of climate threats. Our results indicate that harnessing the power of numbers could increase public trust and concern regarding this defining issue of our time. Communicators, however, should also consider counteracting associated negative feelings—that could halt action—by providing feasible solutions to increase people’s self-efficacy.
{"title":"Numeric social-media posts engage people with climate science","authors":"Ellen Peters, David M Markowitz, Ariel Nadratowski, Brittany Shoots-Reinhard","doi":"10.1093/pnasnexus/pgae250","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae250","url":null,"abstract":"Innumeracy (lack of math skills) among non-scientists often leads climate scientists and others to avoid communicating numbers due to concerns that the public will not understand them and may disengage. However, people often report preferring to receive numbers; providing them also can improve decisions. Here, we demonstrated that the presence vs absence of at least one Arabic integer in climate-related social-media posts increased sharing up to 31.7% but, counter to hypothesis, decreased liking of messages 5.2% in two pre-registered observational studies (climate scientists on Twitter, N>8 million Tweets; climate subreddit, N>17,000 posts and comments). We speculated that the decreased liking was due, not to reduced engagement, but to more negative feelings towards climate-related content described with numeric precision. A pre-registered within-participant experiment (N=212) then varied whether climate consequences were described using Arabic integers (e.g., “90%”) or another format (e.g., verbal terms, “almost all”). The presence of Arabic integers about consequences led to more sharing, wanting to find out more, and greater trust and perceptions of an expert messenger; perceived trust and expertise appeared to mediate effects on sharing and wanting to find out more. Arabic integers about consequences again led to more negative feelings about the Tweets as if numbers clarified the dismaying magnitude of climate threats. Our results indicate that harnessing the power of numbers could increase public trust and concern regarding this defining issue of our time. Communicators, however, should also consider counteracting associated negative feelings—that could halt action—by providing feasible solutions to increase people’s self-efficacy.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141509084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1093/pnasnexus/pgae255
Mojhdeh Baghbanbashi, Hadi Shaker Shiran, Ashok Kakkar, Gholamreza Pazuki, Kurt Ristroph
Aqueous two-phase systems (ATPSs) are liquid-liquid equilibria between two aqueous phases that usually contain over 70% water content each, which results in a non-toxic organic solvent-free environment for biological compounds and biomolecules. ATPSs have attracted significant interest in applications for formulating carriers (microparticles, nanoparticles, hydrogels, and polymersomes) which can be prepared using the spontaneous phase separation of ATPS as a driving force, and loaded with a wide range of bioactive materials, including small molecule drugs, proteins, and cells, for delivery applications. This review provides a detailed analysis of various ATPSs, including strategies employed for particle formation, polymerization of droplets in ATPS, phase-guided block copolymer assemblies, and stimulus-responsive carriers. Processes for loading various bioactive payloads are discussed, and applications of these systems for drug delivery are summarized and discussed.
{"title":"Recent advances in drug delivery applications of aqueous two-phase systems","authors":"Mojhdeh Baghbanbashi, Hadi Shaker Shiran, Ashok Kakkar, Gholamreza Pazuki, Kurt Ristroph","doi":"10.1093/pnasnexus/pgae255","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae255","url":null,"abstract":"Aqueous two-phase systems (ATPSs) are liquid-liquid equilibria between two aqueous phases that usually contain over 70% water content each, which results in a non-toxic organic solvent-free environment for biological compounds and biomolecules. ATPSs have attracted significant interest in applications for formulating carriers (microparticles, nanoparticles, hydrogels, and polymersomes) which can be prepared using the spontaneous phase separation of ATPS as a driving force, and loaded with a wide range of bioactive materials, including small molecule drugs, proteins, and cells, for delivery applications. This review provides a detailed analysis of various ATPSs, including strategies employed for particle formation, polymerization of droplets in ATPS, phase-guided block copolymer assemblies, and stimulus-responsive carriers. Processes for loading various bioactive payloads are discussed, and applications of these systems for drug delivery are summarized and discussed.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1093/pnasnexus/pgae258
Bao Tran Truong, Xiaodan Lou, Alessandro Flammini, Filippo Menczer
Social media, seen by some as the modern public square, is vulnerable to manipulation. By controlling inauthentic accounts impersonating humans, malicious actors can amplify disinformation within target communities. The consequences of such operations are difficult to evaluate due to the challenges posed by collecting data and carrying out ethical experiments that would influence online communities. Here we use a social media model that simulates information diffusion in an empirical network to quantify the impacts of adversarial manipulation tactics on the quality of content. We find that the presence of hub accounts, a hallmark of social media, exacerbates the vulnerabilities of online communities to manipulation. Among the explored tactics that bad actors can employ, infiltrating a community is the most likely to make low-quality content go viral. Such harm can be further compounded by inauthentic agents flooding the network with low-quality, yet appealing content, but is mitigated when bad actors focus on specific targets, such as influential or vulnerable individuals. These insights suggest countermeasures that platforms could employ to increase the resilience of social media users to manipulation.
{"title":"Quantifying the vulnerabilities of the online public square to adversarial manipulation tactics","authors":"Bao Tran Truong, Xiaodan Lou, Alessandro Flammini, Filippo Menczer","doi":"10.1093/pnasnexus/pgae258","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae258","url":null,"abstract":"Social media, seen by some as the modern public square, is vulnerable to manipulation. By controlling inauthentic accounts impersonating humans, malicious actors can amplify disinformation within target communities. The consequences of such operations are difficult to evaluate due to the challenges posed by collecting data and carrying out ethical experiments that would influence online communities. Here we use a social media model that simulates information diffusion in an empirical network to quantify the impacts of adversarial manipulation tactics on the quality of content. We find that the presence of hub accounts, a hallmark of social media, exacerbates the vulnerabilities of online communities to manipulation. Among the explored tactics that bad actors can employ, infiltrating a community is the most likely to make low-quality content go viral. Such harm can be further compounded by inauthentic agents flooding the network with low-quality, yet appealing content, but is mitigated when bad actors focus on specific targets, such as influential or vulnerable individuals. These insights suggest countermeasures that platforms could employ to increase the resilience of social media users to manipulation.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1093/pnasnexus/pgae254
Matthias Christandl
A tensor is a multidimensional array of numbers that can be used to store data, encode a computational relation and represent quantum entanglement. In this sense a tensor can be viewed as valuable resource whose transformation can lead to an understanding of structure in data, computational complexity and quantum information. In order to facilitate the understanding of this resource, we propose a family of information-theoretically constructed preorders on tensors, which can be used to compare tensors with each other and to assess the existence of transformations between them. The construction places copies of a given tensor at the edges of a hypergraph and allows transformations at the vertices. A preorder is then induced by the transformations possible in a given growing sequence of hypergraphs. The new family of preorders generalises the asymptotic restriction preorder which Strassen defined in order to study the computational complexity of matrix multiplication. We derive general properties of the preorders and their associated asymptotic notions of tensor rank and view recent results on tensor rank non-additivity, tensor networks and algebraic complexity in this unifying frame. We hope that this work will provide a useful vantage point for exploring tensors in applied mathematics, physics and computer science, but also from a purely mathematical point of view.
{"title":"The tensor as an informational resource","authors":"Matthias Christandl","doi":"10.1093/pnasnexus/pgae254","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae254","url":null,"abstract":"A tensor is a multidimensional array of numbers that can be used to store data, encode a computational relation and represent quantum entanglement. In this sense a tensor can be viewed as valuable resource whose transformation can lead to an understanding of structure in data, computational complexity and quantum information. In order to facilitate the understanding of this resource, we propose a family of information-theoretically constructed preorders on tensors, which can be used to compare tensors with each other and to assess the existence of transformations between them. The construction places copies of a given tensor at the edges of a hypergraph and allows transformations at the vertices. A preorder is then induced by the transformations possible in a given growing sequence of hypergraphs. The new family of preorders generalises the asymptotic restriction preorder which Strassen defined in order to study the computational complexity of matrix multiplication. We derive general properties of the preorders and their associated asymptotic notions of tensor rank and view recent results on tensor rank non-additivity, tensor networks and algebraic complexity in this unifying frame. We hope that this work will provide a useful vantage point for exploring tensors in applied mathematics, physics and computer science, but also from a purely mathematical point of view.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-28DOI: 10.1093/pnasnexus/pgae257
Emanuele Sangiorgio, Matteo Cinelli, Roy Cerqueti, Walter Quattrociocchi
Initially conceived for entertainment, social media platforms have profoundly transformed the dissemination of information and consequently reshaped the dynamics of agenda-setting. In this scenario, understanding the factors that capture audience attention and drive viral content is crucial. Employing Gibrat's Law, which posits that an entity's growth rate is unrelated to its size, we examine the engagement growth dynamics of news outlets on social media. Our analysis includes the Facebook historical data of over a thousand news outlets, encompassing approximately 57 million posts in four European languages from 2008 to the end of 2022. We discover universal growth dynamics according to which news virality is independent of the traditional size of the outlet. Moreover, our analysis reveals a significant long-term impact of news source reliability on engagement growth, with engagement induced by unreliable sources decreasing over time. We conclude the paper by presenting a statistical model replicating the observed growth dynamics.
{"title":"Followers do not dictate the virality of news outlets on social media","authors":"Emanuele Sangiorgio, Matteo Cinelli, Roy Cerqueti, Walter Quattrociocchi","doi":"10.1093/pnasnexus/pgae257","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae257","url":null,"abstract":"Initially conceived for entertainment, social media platforms have profoundly transformed the dissemination of information and consequently reshaped the dynamics of agenda-setting. In this scenario, understanding the factors that capture audience attention and drive viral content is crucial. Employing Gibrat's Law, which posits that an entity's growth rate is unrelated to its size, we examine the engagement growth dynamics of news outlets on social media. Our analysis includes the Facebook historical data of over a thousand news outlets, encompassing approximately 57 million posts in four European languages from 2008 to the end of 2022. We discover universal growth dynamics according to which news virality is independent of the traditional size of the outlet. Moreover, our analysis reveals a significant long-term impact of news source reliability on engagement growth, with engagement induced by unreliable sources decreasing over time. We conclude the paper by presenting a statistical model replicating the observed growth dynamics.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27DOI: 10.1093/pnasnexus/pgae253
Grace A Noppert, Philippa Clarke, Rebecca C Stebbins, Kate A Duchowny, Robert Melendez, Kimberly Rollings, Allison E Aiello
There is growing recognition of the importance of immune health for understanding the origins of aging-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e., aging of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status and biologically-specific measures of immunosenescence. We used data from the U.S. Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Data Archive (NANDA) to examine associations between indicators of neighborhood SES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA: Naïve) CD4+ T cells and CMV Immunoglobulin G (IgG) levels and neighborhood SES. For the CD4+ EMRA: Naïve ratio, each one-percent increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a one-percent increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (β= 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, non-specific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune aging.
{"title":"The embodiment of the neighborhood socioeconomic environment in the architecture of the immune system","authors":"Grace A Noppert, Philippa Clarke, Rebecca C Stebbins, Kate A Duchowny, Robert Melendez, Kimberly Rollings, Allison E Aiello","doi":"10.1093/pnasnexus/pgae253","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae253","url":null,"abstract":"There is growing recognition of the importance of immune health for understanding the origins of aging-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e., aging of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status and biologically-specific measures of immunosenescence. We used data from the U.S. Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Data Archive (NANDA) to examine associations between indicators of neighborhood SES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA: Naïve) CD4+ T cells and CMV Immunoglobulin G (IgG) levels and neighborhood SES. For the CD4+ EMRA: Naïve ratio, each one-percent increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a one-percent increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (β= 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, non-specific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune aging.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1093/pnasnexus/pgae248
Robert M Hazen, Michael L Wong
To what extent are natural evolving systems limited in their potential diversity (i.e., “bounded”) versus unrestricted (“open-ended”)? Minerals provide a quantitative model evolving system, with well documented increases in mineral diversity through multiple stages of planetary evolution over billions of years. A recent framework that unifies behaviors of both biotic and abiotic evolving systems posits that all such systems are characterized by combinatorial richness subject to selection. In the case of minerals, combinatorial richness derives from the possible combinations of chemical elements coupled with permutations of their formulas’ coefficients. Observed mineral species, which are selected for persistence through deep time, represent a miniscule fraction of all possible element configurations. Furthermore, this model predicts that as planetary systems evolve, stable minerals become an ever-smaller fraction of the “possibility space.” A postulate is that “functional information,” defined as the negative log2 of that fraction, must increase as a system evolves. We have tested this hypothesis for minerals by estimating the fraction of all possible chemical formulas observed from one stage of mineral evolution to the next, based on numbers of different essential elements and the maximum chemical formula complexity at each of 9 chronological stages of mineral evolution. We find a monotonic increase in mineral functional information through these 9 stages—a result consistent with the hypothesis. Furthermore, analysis of the chemical formulas of minerals demonstrates that modern Earth may be approaching the maximum limit of functional information for natural mineral systems—a result demonstrating that mineral evolution is not open ended.
{"title":"Open-Ended versus bounded evolution: Mineral evolution as a case study","authors":"Robert M Hazen, Michael L Wong","doi":"10.1093/pnasnexus/pgae248","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae248","url":null,"abstract":"To what extent are natural evolving systems limited in their potential diversity (i.e., “bounded”) versus unrestricted (“open-ended”)? Minerals provide a quantitative model evolving system, with well documented increases in mineral diversity through multiple stages of planetary evolution over billions of years. A recent framework that unifies behaviors of both biotic and abiotic evolving systems posits that all such systems are characterized by combinatorial richness subject to selection. In the case of minerals, combinatorial richness derives from the possible combinations of chemical elements coupled with permutations of their formulas’ coefficients. Observed mineral species, which are selected for persistence through deep time, represent a miniscule fraction of all possible element configurations. Furthermore, this model predicts that as planetary systems evolve, stable minerals become an ever-smaller fraction of the “possibility space.” A postulate is that “functional information,” defined as the negative log2 of that fraction, must increase as a system evolves. We have tested this hypothesis for minerals by estimating the fraction of all possible chemical formulas observed from one stage of mineral evolution to the next, based on numbers of different essential elements and the maximum chemical formula complexity at each of 9 chronological stages of mineral evolution. We find a monotonic increase in mineral functional information through these 9 stages—a result consistent with the hypothesis. Furthermore, analysis of the chemical formulas of minerals demonstrates that modern Earth may be approaching the maximum limit of functional information for natural mineral systems—a result demonstrating that mineral evolution is not open ended.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1093/pnasnexus/pgae249
Christian Behlendorf, Maurice Diwo, Meina Neumann-Schaal, Manuela Fuchs, Dominik Körner, Lothar Jänsch, Franziska Faber, Wulf Blankenfeldt
Stickland fermentation, the coupled oxidation and reduction of amino acid pairs, is a major pathway for obtaining energy in the nosocomial bacterium Clostridioides difficile. D-proline is the preferred substrate for the reductive path, making it not only a key component of the general metabolism but also impacting on the expression of the clostridial toxins TcdA and TcdB. D-proline reduction is catalyzed by the proline reductase Prd, which belongs to the pyruvoyl-dependent enzymes. These enzymes are translated as inactive proenzymes and require subsequent processing to install the covalently bound pyruvate. Whereas pyruvoyl formation by intramolecular serinolysis has been studied in unrelated enzymes, details about pyruvoyl generation by cysteinolysis as in Prd are lacking. Here we show that Prd maturation requires a small dimeric protein that we have named PrdH. PrdH (CD630_32430) is co-encoded with the PrdA and PrdB subunits of Prd and also found in species producing similar reductases. By producing stable variants of PrdA and PrdB, we demonstrate that PrdH-mediated cleavage and pyruvoyl formation in the PrdA subunit requires PrdB, which can be harnessed to produce active recombinant Prd for subsequent analyses. We further created PrdA- and PrdH-mutants to get insight into the interaction of the components and into the processing reaction itself. Finally, we show that deletion of prdH renders C. difficile insensitive to proline concentrations in culture media, suggesting that this processing factor is essential for proline utilization. Due to the link between Stickland fermentation and pathogenesis, we suggest PrdH may be an attractive target for drug development.
{"title":"Formation of the pyruvoyl-dependent proline reductase Prd from Clostridioides difficile requires the maturation enzyme PrdH","authors":"Christian Behlendorf, Maurice Diwo, Meina Neumann-Schaal, Manuela Fuchs, Dominik Körner, Lothar Jänsch, Franziska Faber, Wulf Blankenfeldt","doi":"10.1093/pnasnexus/pgae249","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae249","url":null,"abstract":"Stickland fermentation, the coupled oxidation and reduction of amino acid pairs, is a major pathway for obtaining energy in the nosocomial bacterium Clostridioides difficile. D-proline is the preferred substrate for the reductive path, making it not only a key component of the general metabolism but also impacting on the expression of the clostridial toxins TcdA and TcdB. D-proline reduction is catalyzed by the proline reductase Prd, which belongs to the pyruvoyl-dependent enzymes. These enzymes are translated as inactive proenzymes and require subsequent processing to install the covalently bound pyruvate. Whereas pyruvoyl formation by intramolecular serinolysis has been studied in unrelated enzymes, details about pyruvoyl generation by cysteinolysis as in Prd are lacking. Here we show that Prd maturation requires a small dimeric protein that we have named PrdH. PrdH (CD630_32430) is co-encoded with the PrdA and PrdB subunits of Prd and also found in species producing similar reductases. By producing stable variants of PrdA and PrdB, we demonstrate that PrdH-mediated cleavage and pyruvoyl formation in the PrdA subunit requires PrdB, which can be harnessed to produce active recombinant Prd for subsequent analyses. We further created PrdA- and PrdH-mutants to get insight into the interaction of the components and into the processing reaction itself. Finally, we show that deletion of prdH renders C. difficile insensitive to proline concentrations in culture media, suggesting that this processing factor is essential for proline utilization. Due to the link between Stickland fermentation and pathogenesis, we suggest PrdH may be an attractive target for drug development.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1093/pnasnexus/pgae237
Linqi Wang, Jin Wang, Kun Zhang, Li Xu
The study of infectious diseases holds significant scientific and societal importance, yet current research on the mechanisms of disease emergence and prediction methods still face challenging issues. This research uses the landscape and flux theoretical framework to reveal the non-equilibrium dynamics of adaptive infectious diseases and uncover its underlying physical mechanism. This allows the quantification of dynamics, characterizing the system with two basins of attraction determined by gradient and rotational flux forces. Quantification of entropy production rates provides insights into the system deviating from equilibrium and associated dissipative costs. The study identifies early warning indicators for the critical transition, emphasizing the advantage of observing time irreversibility from time series over theoretical entropy production and flux. The presence of rotational flux leads to an irreversible pathway between disease states. Through global sensitivity analysis, we identified the key factors influencing infectious diseases. In summary, this research offers valuable insights into infectious disease dynamics and presents a practical approach for predicting the onset of critical transition, addressing existing research gaps.
{"title":"Understanding underlying physical mechanism reveals early warning indicators and key elements for adaptive infections disease networks","authors":"Linqi Wang, Jin Wang, Kun Zhang, Li Xu","doi":"10.1093/pnasnexus/pgae237","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae237","url":null,"abstract":"The study of infectious diseases holds significant scientific and societal importance, yet current research on the mechanisms of disease emergence and prediction methods still face challenging issues. This research uses the landscape and flux theoretical framework to reveal the non-equilibrium dynamics of adaptive infectious diseases and uncover its underlying physical mechanism. This allows the quantification of dynamics, characterizing the system with two basins of attraction determined by gradient and rotational flux forces. Quantification of entropy production rates provides insights into the system deviating from equilibrium and associated dissipative costs. The study identifies early warning indicators for the critical transition, emphasizing the advantage of observing time irreversibility from time series over theoretical entropy production and flux. The presence of rotational flux leads to an irreversible pathway between disease states. Through global sensitivity analysis, we identified the key factors influencing infectious diseases. In summary, this research offers valuable insights into infectious disease dynamics and presents a practical approach for predicting the onset of critical transition, addressing existing research gaps.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Densely packed, motile bacteria can adopt collective states not seen in conventional, passive materials. These states remain in many ways mysterious, and their physical characterization can aid our understanding of natural bacterial colonies and biofilms as well as materials in general. Here, we overcome challenges associated with generating uniformly growing, large, quasi-two-dimensional bacterial assemblies by a membrane-based microfluidic device and report the emergence of glassy states in two-dimensional suspension of Escherichia coli. As the number density increases by cell growth, populations of motile bacteria transition to a glassy state, where cells are packed and unable to move. This takes place in two steps, the first one suppressing only the orientational modes and the second one vitrifying the motion completely. Characterizing each phase through statistical analyses and investigations of individual motion of bacteria, we find not only characteristic features of glass such as rapid slowdown, dynamic heterogeneity and cage effects, but also a few properties distinguished from those of thermal glass. These distinctive properties include the spontaneous formation of micro-domains of aligned cells with collective motion, the appearance of an unusual signal in the dynamic susceptibility, and the dynamic slowdown with a density dependence generally forbidden for thermal systems. Our results are expected to capture general characteristics of such active rod glass, which may serve as a physical mechanism underlying dense bacterial aggregates.
{"title":"Emergence of bacterial glass","authors":"Hisay Lama, Masahiro J Yamamoto, Yujiro Furuta, Takuro Shimaya, Kazumasa A Takeuchi","doi":"10.1093/pnasnexus/pgae238","DOIUrl":"https://doi.org/10.1093/pnasnexus/pgae238","url":null,"abstract":"Densely packed, motile bacteria can adopt collective states not seen in conventional, passive materials. These states remain in many ways mysterious, and their physical characterization can aid our understanding of natural bacterial colonies and biofilms as well as materials in general. Here, we overcome challenges associated with generating uniformly growing, large, quasi-two-dimensional bacterial assemblies by a membrane-based microfluidic device and report the emergence of glassy states in two-dimensional suspension of Escherichia coli. As the number density increases by cell growth, populations of motile bacteria transition to a glassy state, where cells are packed and unable to move. This takes place in two steps, the first one suppressing only the orientational modes and the second one vitrifying the motion completely. Characterizing each phase through statistical analyses and investigations of individual motion of bacteria, we find not only characteristic features of glass such as rapid slowdown, dynamic heterogeneity and cage effects, but also a few properties distinguished from those of thermal glass. These distinctive properties include the spontaneous formation of micro-domains of aligned cells with collective motion, the appearance of an unusual signal in the dynamic susceptibility, and the dynamic slowdown with a density dependence generally forbidden for thermal systems. Our results are expected to capture general characteristics of such active rod glass, which may serve as a physical mechanism underlying dense bacterial aggregates.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141512885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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