Amelia C. Wood, Edwin C. Johnson, Ram R. R. Prasad, Mark V. Sullivan, Nicholas W. Turner, Steven P. Armes, Sarah S. Staniland, Jonathan A. Foster
Peptides are important biomarkers for various diseases, however distinguishing specific amino-acid sequences using artificial receptors remains a major challenge in biomedical sensing. This study introduces a new approach for creating highly selective recognition surfaces using phage display biopanning against metal–organic nanosheets (MONs). Three MONs (ZIF-7, ZIF-7-NH2, and Hf-BTB-NH2) are added to a solution containing every possible combination of seven-residue peptides attached to bacteriophage hosts. The highest affinity peptides for each MON are isolated through successive bio-panning rounds. Comparison of the surface properties of the MONs and high-affinity peptides provide useful insights into the relative importance of electrostatic, hydrophobic, and co-ordination bonding interactions in each system, aiding the design of future MONs. Coating of the Hf-BTB-NH2 MONs onto a quartz crystal microbalance (QCM) produced a five-fold higher signal for phage with the on-target peptide sequence compared to those with generic sequences. Surface plasmon resonance (SPR) studies produce a 4600-fold higher equilibrium dissociation constant (KD) for on-target sequences and are comparable to those of antibodies (KD = 4 x 10−10m). It is anticipated that insights from the biopanning approach, combined with the highly tunable nature of MONs, will lead to a new generation of highly selective recognition surfaces for use in biomedical sensors.
肽是各种疾病的重要生物标志物，但利用人工受体区分特定氨基酸序列仍是生物医学传感领域的一大挑战。本研究介绍了一种针对金属有机纳米片（MONs）使用噬菌体展示生物平移来创建高选择性识别表面的新方法。将三种 MON（ZIF-7、ZIF-7-NH2 和 Hf-BTB-NH2）添加到含有附在噬菌体宿主上的七残基肽的各种可能组合的溶液中。通过连续的生物筛选，分离出每种 MON 的最高亲和力肽。通过比较 MON 和高亲和力肽的表面特性，可以深入了解静电、疏水和配位键相互作用在每个系统中的相对重要性，从而有助于未来 MON 的设计。将 Hf-BTB-NH2 MONs 涂覆在石英晶体微天平（QCM）上，与普通序列的噬菌体相比，具有目标肽序列的噬菌体产生的信号高出五倍。表面等离子体共振（SPR）研究显示，目标序列的平衡解离常数（KD）高出 4600 倍，与抗体的平衡解离常数（KD = 4 x 10-10 m）相当。预计生物平移方法的见解与 MONs 的高可调性相结合，将产生用于生物医学传感器的新一代高选择性识别表面。
{"title":"Phage Display Against 2D Metal–Organic Nanosheets as a New Route to Highly Selective Biomolecular Recognition Surfaces","authors":"Amelia C. Wood, Edwin C. Johnson, Ram R. R. Prasad, Mark V. Sullivan, Nicholas W. Turner, Steven P. Armes, Sarah S. Staniland, Jonathan A. Foster","doi":"10.1002/smll.202406339","DOIUrl":"https://doi.org/10.1002/smll.202406339","url":null,"abstract":"Peptides are important biomarkers for various diseases, however distinguishing specific amino-acid sequences using artificial receptors remains a major challenge in biomedical sensing. This study introduces a new approach for creating highly selective recognition surfaces using phage display biopanning against metal–organic nanosheets (MONs). Three MONs (ZIF-7, ZIF-7-NH<sub>2,</sub> and Hf-BTB-NH<sub>2</sub>) are added to a solution containing every possible combination of seven-residue peptides attached to bacteriophage hosts. The highest affinity peptides for each MON are isolated through successive bio-panning rounds. Comparison of the surface properties of the MONs and high-affinity peptides provide useful insights into the relative importance of electrostatic, hydrophobic, and co-ordination bonding interactions in each system, aiding the design of future MONs. Coating of the Hf-BTB-NH<sub>2</sub> MONs onto a quartz crystal microbalance (QCM) produced a five-fold higher signal for phage with the on-target peptide sequence compared to those with generic sequences. Surface plasmon resonance (SPR) studies produce a 4600-fold higher equilibrium dissociation constant (<i>K<sub>D</sub></i>) for on-target sequences and are comparable to those of antibodies (K<i><sub>D</sub></i> = 4 x 10<sup>−10</sup> <span>m</span>). It is anticipated that insights from the biopanning approach, combined with the highly tunable nature of MONs, will lead to a new generation of highly selective recognition surfaces for use in biomedical sensors.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"6 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The pathogenesis of two major pathogenic characters—amyloid beta (Aβ) accumulation and hyperphosphorylated tau protein—in the brains of patients with Alzheimer's disease (AD) remains unclear.
{"title":"Thorase deficiency causes both Aβ accumulation and tau hyperphosphorylation in mouse brain","authors":"Han Zhang, Menghua Cai, Fei Gao, Jia Yang, Chao Li, Jingyi Han, Yue Wang, Yi Xu, Yu Hu, Hui Chen, Wei He, Jianmin Zhang","doi":"10.1002/alz.14329","DOIUrl":"https://doi.org/10.1002/alz.14329","url":null,"abstract":"The pathogenesis of two major pathogenic characters—amyloid beta (Aβ) accumulation and hyperphosphorylated tau protein—in the brains of patients with Alzheimer's disease (AD) remains unclear.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"20 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Volkmer, Emily Viega Alves, Hagit Bar-Zeev, Elena Barbieri, Petronilla Battista, Ashleigh Beales, Barbara Costa Beber, Emilie Brotherhood, Ines Ribeiro Cadorio, Maria Teresa Carthery-Goulart, Jade Cartwright, Sebastian Crutch, Karen Croot, Maria Isabel d´Ávila Freitas, Jeanne Gallée, Stephanie M. Grasso, Katarina Haley, Heleen Hendriksen, Shalom Henderson, Lize Jiskoot, Isabel Junqueira Almeida, Jackie Kindell, Rachel Kingma, Lorinda LY Kwan-Chen, Monica Lavoie, Adi Lifshitz-Ben-Basat, Regina Jokel, Aurore Mahut-Dubos, Jordi A. Matias-Guiu, Michèle Masson-Trottier, Marcus Meinzer, Ellen McGowan, Carolina Mendez-Orellana, Aaron M. Meyer, Carly Millanski, Núria Montagut, Aimee Mooney, Darby J. Morhardt, Lyndsey Nickels, Monica Norvik, Iris Edda Nowenstein, Avanthi Paplikar, Margaret Pozzebon, Antoine Renard, Leanne Ruggero, Emily Rogalski, Anna U. Rysop, Fredrik Sand Aronsson, Aida Suárez-González, Sharon Savage, Mai Tran Thi, Kyriana Tsapkini, Cathleen Taylor-Rubin, Donna C. Tippett, Nina Unger, Lizet van Ewijk, Sandra Wielaert, Ingvild Elisabeth Winsnes, Anne Whitworth, Ibrahim Can Yasa, David Copland, Maya L. Henry, Jason D. Warren, Rosemary Varley, Sarah J. Wallace, Chris J. D. Hardy
Interventions to treat speech-language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention.
{"title":"An international core outcome set for primary progressive aphasia (COS-PPA): Consensus-based recommendations for communication interventions across research and clinical settings","authors":"Anna Volkmer, Emily Viega Alves, Hagit Bar-Zeev, Elena Barbieri, Petronilla Battista, Ashleigh Beales, Barbara Costa Beber, Emilie Brotherhood, Ines Ribeiro Cadorio, Maria Teresa Carthery-Goulart, Jade Cartwright, Sebastian Crutch, Karen Croot, Maria Isabel d´Ávila Freitas, Jeanne Gallée, Stephanie M. Grasso, Katarina Haley, Heleen Hendriksen, Shalom Henderson, Lize Jiskoot, Isabel Junqueira Almeida, Jackie Kindell, Rachel Kingma, Lorinda LY Kwan-Chen, Monica Lavoie, Adi Lifshitz-Ben-Basat, Regina Jokel, Aurore Mahut-Dubos, Jordi A. Matias-Guiu, Michèle Masson-Trottier, Marcus Meinzer, Ellen McGowan, Carolina Mendez-Orellana, Aaron M. Meyer, Carly Millanski, Núria Montagut, Aimee Mooney, Darby J. Morhardt, Lyndsey Nickels, Monica Norvik, Iris Edda Nowenstein, Avanthi Paplikar, Margaret Pozzebon, Antoine Renard, Leanne Ruggero, Emily Rogalski, Anna U. Rysop, Fredrik Sand Aronsson, Aida Suárez-González, Sharon Savage, Mai Tran Thi, Kyriana Tsapkini, Cathleen Taylor-Rubin, Donna C. Tippett, Nina Unger, Lizet van Ewijk, Sandra Wielaert, Ingvild Elisabeth Winsnes, Anne Whitworth, Ibrahim Can Yasa, David Copland, Maya L. Henry, Jason D. Warren, Rosemary Varley, Sarah J. Wallace, Chris J. D. Hardy","doi":"10.1002/alz.14362","DOIUrl":"https://doi.org/10.1002/alz.14362","url":null,"abstract":"Interventions to treat speech-language difficulties in primary progressive aphasia (PPA) often use word accuracy as a highly comparable outcome. However, there are more constructs of importance to people with PPA that have received less attention.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"80 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1038/s41559-024-02577-4
Simon Aubé, Christian R. Landry
Experiments in budding yeast reveal how the effects of mutations on phenotype and fitness vary across environments.
芽殖酵母的实验揭示了突变对表型和适应性的影响在不同环境下的差异。
{"title":"How genotype-by-environment interactions on fitness emerge","authors":"Simon Aubé, Christian R. Landry","doi":"10.1038/s41559-024-02577-4","DOIUrl":"https://doi.org/10.1038/s41559-024-02577-4","url":null,"abstract":"Experiments in budding yeast reveal how the effects of mutations on phenotype and fitness vary across environments.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"42 1","pages":""},"PeriodicalIF":16.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yini Chen, Yiwei Qi, Yiying Hu, Xinhui Qiu, Tao Qiu, Song Li, Meichen Liu, Qiqi Jia, Bo Sun, Cong Liu, Tianbai Li, Weidong Le
Pathological and neuroimaging alterations in the cerebellum of Alzheimer's disease (AD) patients have been documented. However, the role of cerebellum-derived radiomic and structural connectome modeling in the prediction of AD progression remains unclear.
{"title":"Integrated cerebellar radiomic-network model for predicting mild cognitive impairment in Alzheimer's disease","authors":"Yini Chen, Yiwei Qi, Yiying Hu, Xinhui Qiu, Tao Qiu, Song Li, Meichen Liu, Qiqi Jia, Bo Sun, Cong Liu, Tianbai Li, Weidong Le","doi":"10.1002/alz.14361","DOIUrl":"https://doi.org/10.1002/alz.14361","url":null,"abstract":"Pathological and neuroimaging alterations in the cerebellum of Alzheimer's disease (AD) patients have been documented. However, the role of cerebellum-derived radiomic and structural connectome modeling in the prediction of AD progression remains unclear.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"34 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul Aisen, Randall J. Bateman, Damian Crowther, Jeff Cummings, John Dwyer, Takeshi Iwatsubo, Marie Kosco-Vilbois, Eric McDade, Richard Mohs, Philip Scheltens, Reisa Sperling, Dennis Selkoe
Decades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta-protein (Aβ). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease-modifying Aβ antibody for early AD. Secondary prevention trials with Aβ antibodies are underway. We summarize peer-reviewed evidence for targeting Aβ and argue that regulators should consider approving new agents working by similar mechanisms (Aβ antibodies and vaccines) based on robust amyloid lowering and reasonable safety. The urgent need to provide treatments to millions of mildly symptomatic patients suggests that AD should join other diseases for which standard approval is based on significant changes in mechanistically meaningful biomarkers coupled with safety. Robust amyloid lowering in secondary prevention trials of people who have amyloid plaques but are asymptomatic could also provide evidence of a change in the pathophysiological progression of AD as a basis for regulatory approval.
数十年的研究证明，阿尔茨海默病（AD）的部分病因是淀粉样β蛋白（Aβ）在大脑中的积累。2023 年，美国食品和药物管理局全面批准了一种可改变疾病的 Aβ 抗体用于早期 AD 的治疗。Aβ抗体的二级预防试验正在进行中。我们总结了针对 Aβ 的同行评审证据，并认为监管机构应考虑批准通过类似机制发挥作用的新药（Aβ 抗体和疫苗），这些新药应具有强有力的淀粉样蛋白降低作用和合理的安全性。为数百万症状轻微的患者提供治疗的迫切需要表明，注意力缺失症也应加入其他疾病的行列，这些疾病的标准审批依据是机理上有意义的生物标志物的显著变化以及安全性。在对有淀粉样蛋白斑块但无症状的患者进行的二级预防试验中，降低淀粉样蛋白水平的药物也能提供证据，证明AD的病理生理进展发生了变化，从而为监管机构批准提供依据。
{"title":"The case for regulatory approval of amyloid-lowering immunotherapies in Alzheimer's disease based on clearcut biomarker evidence","authors":"Paul Aisen, Randall J. Bateman, Damian Crowther, Jeff Cummings, John Dwyer, Takeshi Iwatsubo, Marie Kosco-Vilbois, Eric McDade, Richard Mohs, Philip Scheltens, Reisa Sperling, Dennis Selkoe","doi":"10.1002/alz.14342","DOIUrl":"https://doi.org/10.1002/alz.14342","url":null,"abstract":"Decades of research have provided evidence that Alzheimer's disease (AD) is caused in part by cerebral accumulation of amyloid beta-protein (Aβ). In 2023, the US Food and Drug Administration gave full regulatory approval to a disease-modifying Aβ antibody for early AD. Secondary prevention trials with Aβ antibodies are underway. We summarize peer-reviewed evidence for targeting Aβ and argue that regulators should consider approving new agents working by similar mechanisms (Aβ antibodies and vaccines) based on robust amyloid lowering and reasonable safety. The urgent need to provide treatments to millions of mildly symptomatic patients suggests that AD should join other diseases for which standard approval is based on significant changes in mechanistically meaningful biomarkers coupled with safety. Robust amyloid lowering in secondary prevention trials of people who have amyloid plaques but are asymptomatic could also provide evidence of a change in the pathophysiological progression of AD as a basis for regulatory approval.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"3 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ariel Caviedes, Paulina Orellana, Cristian Ávila-Rincón, Agustín Ibáñez, Michael J. Corley, Hernando Santamaría-García, Claudia Duran-Aniotz, Carolina Ochoa-Rosales
<p>Dementia is a major health issue in Latin America and the Caribbean (LAC), with a prevalence of 9.5% and an incidence of 26.0 per 1000 among people over 60 years. With cases expected to triple by 2050, there is an urgent need for more extensive local research in this field.<span><sup>1</sup></span> Despite advancements in neuroimaging and protein biomarkers, significant gaps remain in understanding how biological mechanisms that interact with LAC-specific environmental exposures influence dementia risk, presentation, and treatment. Interactions between genetic and environmental factors, mainly through epigenetic changes including DNA methylation (DNAm), noncoding RNA, and histone modifications, can modulate gene expression, altering molecular traits and health outcomes.<span><sup>2</sup></span> Adverse environmental exposures in LAC, including socioeconomic disparities, pollutants, unhealthy habits, and comorbidities, have been associated with higher dementia risk,<span><sup>1</sup></span> potentially through epigenetic mechanisms. Most existing knowledge on epigenetics is derived from studies conducted in Europe and the United States, which limits the generalization of these findings to underrepresented regions,<span><sup>3</sup></span> including LAC. To understand state-of-the-art epigenetic studies on dementia in LAC, we conducted a systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocols. Our search focused on chemical modifications of the DNA or histones able to regulate chromatin's structure. We reviewed the literature up to May 2024 in MEDLINE, Web of Science, PubMed, and Scopus databases (research strategy and findings in Table 1). Surprisingly, we found only five case-control studies comparing late-onset Alzheimer's disease (LOAD)<span><sup>4-6</sup></span> or mild cognitive impairment (MCI)<span><sup>7, 8</sup></span> versus healthy controls, revealing a disparity in published studies on epigenetics and dementia in LAC. Further epigenetics research is needed in the region, including the use of cutting-edge methods, target tissues, and systematic approaches. Studies have investigated global DNAm (<i>LINE-1</i>).<span><sup>4</sup></span> DNAm in candidate genes.<span><sup>5, 6</sup></span> or genome-wide DNAm<span><sup>7, 8</sup></span> assessed in peripheral blood. Two studies were conducted in Colombian,<span><sup>4, 5</sup></span> two in Mexican-American (MA),<span><sup>7, 8</sup></span> and one in Costa Rican populations.<span><sup>6</sup></span> Three studies addressed sex<span><sup>4, 5</sup></span> or ethnic<span><sup>8</sup></span> differences in DNAm. The study conducted by Hernández et al. found no significant differences in <i>LINE-1</i> methylation across LOAD patients and controls, even after stratification by sex or <i>APOE4</i> genotypes.<span><sup>4</sup></span> Further, Salcedo-Tacuma et al. identified significantly lower DNAm levels at three CpGs at <i>BIN1<
{"title":"Epigenetics of dementia remains unraveled in Latin American and Caribbean populations: A call for collaborative efforts","authors":"Ariel Caviedes, Paulina Orellana, Cristian Ávila-Rincón, Agustín Ibáñez, Michael J. Corley, Hernando Santamaría-García, Claudia Duran-Aniotz, Carolina Ochoa-Rosales","doi":"10.1002/alz.14295","DOIUrl":"https://doi.org/10.1002/alz.14295","url":null,"abstract":"<p>Dementia is a major health issue in Latin America and the Caribbean (LAC), with a prevalence of 9.5% and an incidence of 26.0 per 1000 among people over 60 years. With cases expected to triple by 2050, there is an urgent need for more extensive local research in this field.<span><sup>1</sup></span> Despite advancements in neuroimaging and protein biomarkers, significant gaps remain in understanding how biological mechanisms that interact with LAC-specific environmental exposures influence dementia risk, presentation, and treatment. Interactions between genetic and environmental factors, mainly through epigenetic changes including DNA methylation (DNAm), noncoding RNA, and histone modifications, can modulate gene expression, altering molecular traits and health outcomes.<span><sup>2</sup></span> Adverse environmental exposures in LAC, including socioeconomic disparities, pollutants, unhealthy habits, and comorbidities, have been associated with higher dementia risk,<span><sup>1</sup></span> potentially through epigenetic mechanisms. Most existing knowledge on epigenetics is derived from studies conducted in Europe and the United States, which limits the generalization of these findings to underrepresented regions,<span><sup>3</sup></span> including LAC. To understand state-of-the-art epigenetic studies on dementia in LAC, we conducted a systematic review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocols. Our search focused on chemical modifications of the DNA or histones able to regulate chromatin's structure. We reviewed the literature up to May 2024 in MEDLINE, Web of Science, PubMed, and Scopus databases (research strategy and findings in Table 1). Surprisingly, we found only five case-control studies comparing late-onset Alzheimer's disease (LOAD)<span><sup>4-6</sup></span> or mild cognitive impairment (MCI)<span><sup>7, 8</sup></span> versus healthy controls, revealing a disparity in published studies on epigenetics and dementia in LAC. Further epigenetics research is needed in the region, including the use of cutting-edge methods, target tissues, and systematic approaches. Studies have investigated global DNAm (<i>LINE-1</i>).<span><sup>4</sup></span> DNAm in candidate genes.<span><sup>5, 6</sup></span> or genome-wide DNAm<span><sup>7, 8</sup></span> assessed in peripheral blood. Two studies were conducted in Colombian,<span><sup>4, 5</sup></span> two in Mexican-American (MA),<span><sup>7, 8</sup></span> and one in Costa Rican populations.<span><sup>6</sup></span> Three studies addressed sex<span><sup>4, 5</sup></span> or ethnic<span><sup>8</sup></span> differences in DNAm. The study conducted by Hernández et al. found no significant differences in <i>LINE-1</i> methylation across LOAD patients and controls, even after stratification by sex or <i>APOE4</i> genotypes.<span><sup>4</sup></span> Further, Salcedo-Tacuma et al. identified significantly lower DNAm levels at three CpGs at <i>BIN1<","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"72 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1038/s41559-024-02582-7
Mohammad A. Siddiq, Fabien Duveau, Patricia J. Wittkopp
The environment influences how an organism’s genotype determines its phenotype and how this phenotype affects its fitness. Here, to better understand this dual role of environment in the production and selection of phenotypic variation, we determined genotype–phenotype–fitness relationships for mutant strains of Saccharomyces cerevisiae in four environments. Specifically, we measured how promoter mutations of the metabolic gene TDH3 modified expression level and affected growth for four different carbon sources. In each environment, we observed a clear relationship between TDH3 expression level and fitness, but this relationship differed among environments. Mutations with similar effects on expression in different environments often had different effects on fitness and vice versa. Such environment-specific relationships between phenotype and fitness can shape the evolution of phenotypic plasticity. We also found that mutations disrupting binding sites for transcription factors had more variable effects on expression among environments than those disrupting the TATA box, which is part of the core promoter. However, mutations with the most environmentally variable effects on fitness were located in the TATA box, because of both the lack of plasticity of TATA box mutations and environment-specific fitness functions. This observation suggests that mutations affecting different molecular mechanisms contribute unequally to regulatory sequence evolution in changing environments.
{"title":"Plasticity and environment-specific relationships between gene expression and fitness in Saccharomyces cerevisiae","authors":"Mohammad A. Siddiq, Fabien Duveau, Patricia J. Wittkopp","doi":"10.1038/s41559-024-02582-7","DOIUrl":"https://doi.org/10.1038/s41559-024-02582-7","url":null,"abstract":"<p>The environment influences how an organism’s genotype determines its phenotype and how this phenotype affects its fitness. Here, to better understand this dual role of environment in the production and selection of phenotypic variation, we determined genotype–phenotype–fitness relationships for mutant strains of <i>Saccharomyces cerevisiae</i> in four environments. Specifically, we measured how promoter mutations of the metabolic gene <i>TDH3</i> modified expression level and affected growth for four different carbon sources. In each environment, we observed a clear relationship between <i>TDH3</i> expression level and fitness, but this relationship differed among environments. Mutations with similar effects on expression in different environments often had different effects on fitness and vice versa. Such environment-specific relationships between phenotype and fitness can shape the evolution of phenotypic plasticity. We also found that mutations disrupting binding sites for transcription factors had more variable effects on expression among environments than those disrupting the TATA box, which is part of the core promoter. However, mutations with the most environmentally variable effects on fitness were located in the TATA box, because of both the lack of plasticity of TATA box mutations and environment-specific fitness functions. This observation suggests that mutations affecting different molecular mechanisms contribute unequally to regulatory sequence evolution in changing environments.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"80 1","pages":""},"PeriodicalIF":16.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Electromethanation of CO2 has received intensive attention due to its high calorific value and convenient storage along with transportation to accommodate industrial demands. However, it is limited by sluggish multi-step proton-coupled electron transfer kinetics and undesired *H coupling under high current density, posing great challenges to its commercialization. Herein, carbon nitride (CN) with superior hydrogen adsorption ability is used as an active-hydrogen adsorption and supply material. Through a facile liquid-assisted exfoliation and electrostatic self-assembly strategy to strengthen its interfacial contacts with Cu2O catalysts, yielding a strengthened CH4 production 52 times higher than that of pristine Cu2O. Flow-cell test ultimately achieved FECH4 and remarkably CH4 partial current density of 61% and 561 mA cm−2, respectively. With in situ ATR-FTIR spectra and DFT calculations, it is established that strengthened interfaces enabled abundant *H tethered by ─C─N═C─ sites in CN nanosheets and oriented to the *CO hydrogenation to *CHO and *CHx on Cu species. This work reveals the profound influence of fine-expanded interfaces with dimensional materials on the product distribution and yield through the active-hydrogen management, which is of reference value for other small-molecule electro-polarization dominated by the proton-coupled electron transfer (PCET) process (e.g., N2, O2, etc.).
{"title":"Large-Current CO2 Electromethanation Through Active Hydrogen Regulation Over Carbon Nitride","authors":"Tianxiang Yan, Yaxin Jin, Qun Fan, Hai Liu, Xindi Li, Tianying Zhang, Hui Wang, Jianlong Lin, Haoyuan Chi, Sheng Zhang, Xinbin Ma","doi":"10.1002/smll.202408600","DOIUrl":"https://doi.org/10.1002/smll.202408600","url":null,"abstract":"Electromethanation of CO<sub>2</sub> has received intensive attention due to its high calorific value and convenient storage along with transportation to accommodate industrial demands. However, it is limited by sluggish multi-step proton-coupled electron transfer kinetics and undesired <sup>*</sup>H coupling under high current density, posing great challenges to its commercialization. Herein, carbon nitride (CN) with superior hydrogen adsorption ability is used as an active-hydrogen adsorption and supply material. Through a facile liquid-assisted exfoliation and electrostatic self-assembly strategy to strengthen its interfacial contacts with Cu<sub>2</sub>O catalysts, yielding a strengthened CH<sub>4</sub> production 52 times higher than that of pristine Cu<sub>2</sub>O. Flow-cell test ultimately achieved FE<sub>CH4</sub> and remarkably CH<sub>4</sub> partial current density of 61% and 561 mA cm<sup>−2</sup>, respectively. With in situ ATR-FTIR spectra and DFT calculations, it is established that strengthened interfaces enabled abundant <sup>*</sup>H tethered by ─C─N═C─ sites in CN nanosheets and oriented to the <sup>*</sup>CO hydrogenation to <sup>*</sup>CHO and <sup>*</sup>CHx on Cu species. This work reveals the profound influence of fine-expanded interfaces with dimensional materials on the product distribution and yield through the active-hydrogen management, which is of reference value for other small-molecule electro-polarization dominated by the proton-coupled electron transfer (PCET) process (e.g., N<sub>2</sub>, O<sub>2</sub>, etc.).","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"69 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heavy atom effects can be used to enhance intermolecular interaction, regulate quinoidal resonance properties, increase bandwidths, and tune diradical characters, which have significant impacts on organic optoelectronic devices, such as organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), etc. Meanwhile, the introduction of heavy atoms is shown to promote charge transfer, enhance air stability, and improve device performances in the field of organic thermoelectrics (OTEs). Thus, heavy atom effects are receiving more and more attention. However, regulating heavy atoms in organic semiconductors is still meeting great challenges. For example, heavy atoms will lead to solubility and stability issues (tellurium substitution) and lack of versatile design strategy and effective synthetic methods to be incorporated into organic semiconductors, which limit their application in electronic devices. Therefore, this work timely summarizes the unique functionalities of heavy atom effects, and up-to-date progress in organic electronics including OFETs, OPVs, OLEDs, and OTEs, while the structure-performance relationships between molecular designs and electronic devices are clearly elucidated. Furthermore, this review systematically analyzes the remaining challenges in regulating heavy atoms within organic semiconductors, and design strategies toward efficient and stable organic semiconductors by the introduction of novel heavy atoms regulation are proposed.
{"title":"Regulating Optoelectronic and Thermoelectric Properties of Organic Semiconductors by Heavy Atom Effects","authors":"Hao He, Ziting Zhong, Peng Fan, Wenchao Zhao, Dafei Yuan","doi":"10.1002/smll.202405156","DOIUrl":"https://doi.org/10.1002/smll.202405156","url":null,"abstract":"Heavy atom effects can be used to enhance intermolecular interaction, regulate quinoidal resonance properties, increase bandwidths, and tune diradical characters, which have significant impacts on organic optoelectronic devices, such as organic field-effect transistors (OFETs), organic light-emitting diodes (OLEDs), organic photovoltaics (OPVs), etc. Meanwhile, the introduction of heavy atoms is shown to promote charge transfer, enhance air stability, and improve device performances in the field of organic thermoelectrics (OTEs). Thus, heavy atom effects are receiving more and more attention. However, regulating heavy atoms in organic semiconductors is still meeting great challenges. For example, heavy atoms will lead to solubility and stability issues (tellurium substitution) and lack of versatile design strategy and effective synthetic methods to be incorporated into organic semiconductors, which limit their application in electronic devices. Therefore, this work timely summarizes the unique functionalities of heavy atom effects, and up-to-date progress in organic electronics including OFETs, OPVs, OLEDs, and OTEs, while the structure-performance relationships between molecular designs and electronic devices are clearly elucidated. Furthermore, this review systematically analyzes the remaining challenges in regulating heavy atoms within organic semiconductors, and design strategies toward efficient and stable organic semiconductors by the introduction of novel heavy atoms regulation are proposed.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"72 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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