Pub Date : 2024-03-29eCollection Date: 2024-03-01DOI: 10.59249/WMGE9032
Tatjana L Kay, Margaret C Moulson, Simone N Vigod, Nour Schoueri-Mychasiw, Daisy R Singla
Social support refers to the help someone receives emotionally or instrumentally from their social network. Poor social support in the perinatal period has been associated with increased risk for symptoms of common mental disorders, including depression and posttraumatic stress symptoms (PTS), which may impact parenting behavior. Whether social support impacts parenting behaviors, independent of mental health symptomatology, remains unclear. Among N=309 participants of the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT Trial), a large perinatal depression and anxiety treatment trial, we explored the relations between perceived social support, perinatal depressive and PTS symptoms, and psychosocial stimulation provided by the parent in their home environment. Social support was measured at baseline using the Multidimensional Scale of Perceived Social Support (MSPSS). Perinatal depressive symptoms were measured by the Edinburgh Postnatal Depression Scale (EPDS) and PTS symptoms were measured by the Abbreviated PTSD Checklist (PCL-6) at baseline, 3-, and 6-months post-randomization. Psychosocial stimulation was assessed by the Home Observation Measurement of the Environment (HOME) when the infant was between 6 to 24 months. Using stepwise hierarchical regressions, we found: (1) perceived social support at baseline significantly predicted both depressive and PTS symptoms at 3-months post-randomization, even when controlling for baseline depressive and PTS symptoms; and (2) while neither depressive nor PTS symptoms were significantly associated with psychosocial stimulation, perceived social support at baseline was a significant predictor. Clinical implications regarding treatment of perinatal patients are discussed.
{"title":"The Role of Social Support in Perinatal Mental Health and Psychosocial Stimulation.","authors":"Tatjana L Kay, Margaret C Moulson, Simone N Vigod, Nour Schoueri-Mychasiw, Daisy R Singla","doi":"10.59249/WMGE9032","DOIUrl":"10.59249/WMGE9032","url":null,"abstract":"<p><p>Social support refers to the help someone receives emotionally or instrumentally from their social network. Poor social support in the perinatal period has been associated with increased risk for symptoms of common mental disorders, including depression and posttraumatic stress symptoms (PTS), which may impact parenting behavior. Whether social support impacts parenting behaviors, independent of mental health symptomatology, remains unclear. Among N=309 participants of the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT Trial), a large perinatal depression and anxiety treatment trial, we explored the relations between perceived social support, perinatal depressive and PTS symptoms, and psychosocial stimulation provided by the parent in their home environment. Social support was measured at baseline using the Multidimensional Scale of Perceived Social Support (MSPSS). Perinatal depressive symptoms were measured by the Edinburgh Postnatal Depression Scale (EPDS) and PTS symptoms were measured by the Abbreviated PTSD Checklist (PCL-6) at baseline, 3-, and 6-months post-randomization. Psychosocial stimulation was assessed by the Home Observation Measurement of the Environment (HOME) when the infant was between 6 to 24 months. Using stepwise hierarchical regressions, we found: (1) perceived social support at baseline significantly predicted both depressive and PTS symptoms at 3-months post-randomization, even when controlling for baseline depressive and PTS symptoms; and (2) while neither depressive nor PTS symptoms were significantly associated with psychosocial stimulation, perceived social support at baseline was a significant predictor. Clinical implications regarding treatment of perinatal patients are discussed.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"97 1","pages":"3-16"},"PeriodicalIF":2.7,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29eCollection Date: 2024-03-01DOI: 10.59249/MWYW7163
Deanna Nardella
Pregnant individuals and infants in the US are experiencing rising morbidity and mortality rates. Breastfeeding is a cost-effective intervention associated with a lower risk of health conditions driving dyadic morbidity and mortality, including cardiometabolic disease and sudden infant death. Pregnant individuals and infants from racial/ethnic subgroups facing the highest risk of mortality also have the lowest breastfeeding rates, likely reflective of generational socioeconomic marginalization and its impact on health outcomes. Promoting breastfeeding among groups with the lowest rates could improve the health of dyads with the greatest health risk and facilitate more equitable, person-centered lactation outcomes. Multiple barriers to lactation initiation and duration exist for families who have been socioeconomically marginalized by health and public systems. These include the lack of paid parental leave, increased access to subsidized human milk substitutes, and reduced access to professional and lay breastfeeding expertise. Breast pumps have the potential to mitigate these barriers, making breastfeeding more accessible to all interested dyads. In 2012, The Patient Protection and Affordable Care Act (ACA) greatly expanded access to pumps through the preventative services mandate, with a single pump now available to most US families. Despite their near ubiquitous use among lactating individuals, little research has been conducted on how and when to use pumps appropriately to optimize breastfeeding outcomes. There is a timely and critical need for policy, scholarship, and education around pump use given their widespread provision and potential to promote equity for those families facing the greatest barriers to achieving their personal breastfeeding goals.
{"title":"Pumps: A Possible Tool to Promote More Equitable Lactation Outcomes.","authors":"Deanna Nardella","doi":"10.59249/MWYW7163","DOIUrl":"10.59249/MWYW7163","url":null,"abstract":"<p><p>Pregnant individuals and infants in the US are experiencing rising morbidity and mortality rates. Breastfeeding is a cost-effective intervention associated with a lower risk of health conditions driving dyadic morbidity and mortality, including cardiometabolic disease and sudden infant death. Pregnant individuals and infants from racial/ethnic subgroups facing the highest risk of mortality also have the lowest breastfeeding rates, likely reflective of generational socioeconomic marginalization and its impact on health outcomes. Promoting breastfeeding among groups with the lowest rates could improve the health of dyads with the greatest health risk and facilitate more equitable, person-centered lactation outcomes. Multiple barriers to lactation initiation and duration exist for families who have been socioeconomically marginalized by health and public systems. These include the lack of paid parental leave, increased access to subsidized human milk substitutes, and reduced access to professional and lay breastfeeding expertise. Breast pumps have the potential to mitigate these barriers, making breastfeeding more accessible to all interested dyads. In 2012, The Patient Protection and Affordable Care Act (ACA) greatly expanded access to pumps through the preventative services mandate, with a single pump now available to most US families. Despite their near ubiquitous use among lactating individuals, little research has been conducted on how and when to use pumps appropriately to optimize breastfeeding outcomes. There is a timely and critical need for policy, scholarship, and education around pump use given their widespread provision and potential to promote equity for those families facing the greatest barriers to achieving their personal breastfeeding goals.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"97 1","pages":"99-106"},"PeriodicalIF":2.5,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-29eCollection Date: 2024-03-01DOI: 10.59249/NKTK3337
Rebecca Nowland, Joanna Charles, Gill Thomson
Background: Becoming a parent has been highlighted as a period associated with increased risks for loneliness, with around one-third of parents reporting feeling lonely often or always. However, as most understanding of loneliness is based on elderly or student cohorts, further insights into the costs of parental loneliness is needed. Method: We conducted a literature review of impacts of loneliness in pregnancy and parenthood and present a synthesis of the health, social, societal, and economic costs. We draw on evidence about impacts and costs of loneliness in other cohorts to help provide a wider context to understand the impacts and costs and how parental loneliness differs from other populations. Results: Similar to literature with elderly cohorts, parental loneliness has impacts on health and wellbeing, such as depression in new parents and increased general practitioner (GP) visits in pregnancy. But also has intergenerational impacts via its association with poor mental health and social competence and increased respiratory tract infections in the child. Physical health impacts widely associated with loneliness in other cohorts have yet to be examined in parents. Loneliness in parents is likely to result in social withdrawal further isolating parents and wider societal and economic costs relating to absence from employment and informal caring roles. Conclusion: Parental loneliness has the potential for negative and pervasive impacts. As parental loneliness has wide ranging and intergenerational impacts it is important that a multi-sectoral perspective is used when examining its costs.
{"title":"Loneliness in Pregnancy and Parenthood: Impacts, Outcomes, and Costs.","authors":"Rebecca Nowland, Joanna Charles, Gill Thomson","doi":"10.59249/NKTK3337","DOIUrl":"10.59249/NKTK3337","url":null,"abstract":"<p><p><b>Background</b>: Becoming a parent has been highlighted as a period associated with increased risks for loneliness, with around one-third of parents reporting feeling lonely often or always. However, as most understanding of loneliness is based on elderly or student cohorts, further insights into the costs of parental loneliness is needed. <b>Method</b>: We conducted a literature review of impacts of loneliness in pregnancy and parenthood and present a synthesis of the health, social, societal, and economic costs. We draw on evidence about impacts and costs of loneliness in other cohorts to help provide a wider context to understand the impacts and costs and how parental loneliness differs from other populations. <b>Results</b>: Similar to literature with elderly cohorts, parental loneliness has impacts on health and wellbeing, such as depression in new parents and increased general practitioner (GP) visits in pregnancy. But also has intergenerational impacts via its association with poor mental health and social competence and increased respiratory tract infections in the child. Physical health impacts widely associated with loneliness in other cohorts have yet to be examined in parents. Loneliness in parents is likely to result in social withdrawal further isolating parents and wider societal and economic costs relating to absence from employment and informal caring roles. <b>Conclusion</b>: Parental loneliness has the potential for negative and pervasive impacts. As parental loneliness has wide ranging and intergenerational impacts it is important that a multi-sectoral perspective is used when examining its costs.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"97 1","pages":"93-98"},"PeriodicalIF":2.7,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29eCollection Date: 2023-12-01DOI: 10.59249/FBHI3484
Grant Ramsey, Pierre M Durand
Theoretical frameworks concerning cell fate typically center on proximate causes to explain how cells know what type they are meant to become. While major advances in cell fate theory have been achieved by these mechanism-focused frameworks, there are some aspects of cell decision-making that require an evolutionary interpretation. While mechanistic biologists sometimes turn to evolutionary theory to gain insights about cell fate (cancer is a good example), it is not entirely clear in cell fate theory what insights evolutionary theory can add, and why in some cases it is required for understanding cell fate. In this perspective we draw on our work on cellular mortality to illustrate how evolutionary theory provides an explanation for death being selected as one of the potential cell fates. Using our hypothesis for why some microbes in a community choose death as their fate, we suggest that some insights in cell fate theory are inaccessible to a theoretical framework that focuses solely on proximate causes.
{"title":"Cell Fate: What's Evolution Got to Do With It?","authors":"Grant Ramsey, Pierre M Durand","doi":"10.59249/FBHI3484","DOIUrl":"10.59249/FBHI3484","url":null,"abstract":"<p><p>Theoretical frameworks concerning cell fate typically center on proximate causes to explain how cells know what type they are meant to become. While major advances in cell fate theory have been achieved by these mechanism-focused frameworks, there are some aspects of cell decision-making that require an evolutionary interpretation. While mechanistic biologists sometimes turn to evolutionary theory to gain insights about cell fate (cancer is a good example), it is not entirely clear in cell fate theory what insights evolutionary theory can add, and why in some cases it is required for understanding cell fate. In this perspective we draw on our work on cellular mortality to illustrate how evolutionary theory provides an explanation for death being selected as one of the potential cell fates. Using our hypothesis for why some microbes in a community choose death as their fate, we suggest that some insights in cell fate theory are inaccessible to a theoretical framework that focuses solely on proximate causes.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"565-568"},"PeriodicalIF":2.7,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing Our Understanding of Cell Types, Differentiation, and Disease Through Enhancers: An Interview with César Daniel Meléndez-Ramírez, MS.","authors":"Reem Abu-Shamma","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"569-572"},"PeriodicalIF":2.7,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29eCollection Date: 2023-12-01DOI: 10.59249/WPKX7733
Marita A John, Niloufar Pourfarrokh, Jaya Ruth Asirvatham
Although rare, breast metastases can mimic primary tumors, both clinically, radiologically, and histopathologically. Melanoma is a highly metastasizing tumor, and it is known as a great mimicker of tumors. Metastatic melanoma in the breast can mimic primary breast cancer and pose a diagnostic challenge. In most cases, it is associated with disseminated disease and a poor prognosis, therefore, histologic, immunohistochemical and clinical correlation is crucial in diagnosing these cases. In this case report, we discuss a 63-year-old female who presented with clinical features of probable breast cancer, describe immunohistochemistry workup, and discuss pitfalls in interpretation.
{"title":"Melanoma in the Breast: A Diagnostic Challenge.","authors":"Marita A John, Niloufar Pourfarrokh, Jaya Ruth Asirvatham","doi":"10.59249/WPKX7733","DOIUrl":"10.59249/WPKX7733","url":null,"abstract":"<p><p>Although rare, breast metastases can mimic primary tumors, both clinically, radiologically, and histopathologically. Melanoma is a highly metastasizing tumor, and it is known as a great mimicker of tumors. Metastatic melanoma in the breast can mimic primary breast cancer and pose a diagnostic challenge. In most cases, it is associated with disseminated disease and a poor prognosis, therefore, histologic, immunohistochemical and clinical correlation is crucial in diagnosing these cases. In this case report, we discuss a 63-year-old female who presented with clinical features of probable breast cancer, describe immunohistochemistry workup, and discuss pitfalls in interpretation.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"475-479"},"PeriodicalIF":2.7,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29eCollection Date: 2023-12-01DOI: 10.59249/RHUF5686
Mugdha Pradhan, Prasad Pethe
Scar formation is a normal response to skin injuries. During the scar-remodeling phase, scar tissue is usually replaced with normal, functional tissue. However, after deep burn injuries, the scar tissue may persist and lead to contractures around joints, a condition known as hypertrophic scar tissue. Unfortunately, current treatment options for hypertrophic scars, such as surgery and pressure garments, often fail to prevent their reappearance. One of the primary challenges in treating hypertrophic scars is a lack of knowledge about the molecular mechanisms underlying their formation. In this review, we critically analyze studies that have attempted to uncover the molecular mechanisms behind hypertrophic scar formation after severe burn injuries, as well as clinical trials conducted to treat post-burn hypertrophic scars. We found that most clinical trials used pressure garments, laser treatments, steroids, and proliferative inhibitors for hypertrophic scars, with outcomes measured using subjective scar scales. However, fundamental research using human burn injury biopsies has shown that pathways such as Transforming Growth factor β (TGFβ), Phosphatase and tensin homolog (PTEN), and Toll-like receptors (TLRs) could be potentially regulated to reduce scarring. Therefore, we conclude that more testing is necessary to determine the efficacy of these molecular targets in reducing hypertrophic scarring. Specifically, double-blinded clinical trials are needed, where the outcomes can be measured with more robust quantitative molecular parameters.
{"title":"The Molecular Mechanisms Involved in the Hypertrophic Scars Post-Burn Injury.","authors":"Mugdha Pradhan, Prasad Pethe","doi":"10.59249/RHUF5686","DOIUrl":"10.59249/RHUF5686","url":null,"abstract":"<p><p>Scar formation is a normal response to skin injuries. During the scar-remodeling phase, scar tissue is usually replaced with normal, functional tissue. However, after deep burn injuries, the scar tissue may persist and lead to contractures around joints, a condition known as hypertrophic scar tissue. Unfortunately, current treatment options for hypertrophic scars, such as surgery and pressure garments, often fail to prevent their reappearance. One of the primary challenges in treating hypertrophic scars is a lack of knowledge about the molecular mechanisms underlying their formation. In this review, we critically analyze studies that have attempted to uncover the molecular mechanisms behind hypertrophic scar formation after severe burn injuries, as well as clinical trials conducted to treat post-burn hypertrophic scars. We found that most clinical trials used pressure garments, laser treatments, steroids, and proliferative inhibitors for hypertrophic scars, with outcomes measured using subjective scar scales. However, fundamental research using human burn injury biopsies has shown that pathways such as Transforming Growth factor β (TGFβ), Phosphatase and tensin homolog (PTEN), and Toll-like receptors (TLRs) could be potentially regulated to reduce scarring. Therefore, we conclude that more testing is necessary to determine the efficacy of these molecular targets in reducing hypertrophic scarring. Specifically, double-blinded clinical trials are needed, where the outcomes can be measured with more robust quantitative molecular parameters.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"549-563"},"PeriodicalIF":2.7,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29eCollection Date: 2023-12-01DOI: 10.59249/UXOH1740
Yizhou Li, Wenli Jiang, Xintong Zhou, Yicen Long, Yujia Sun, Ye Zeng, Xinghong Yao
Micropatterns, characterized as distinct physical microstructures or chemical adhesion matrices on substance surfaces, have emerged as a powerful tool for manipulating cellular activity. By creating specific extracellular matrix microenvironments, micropatterns can influence various cell behaviors, including orientation, proliferation, migration, and differentiation. This review provides a comprehensive overview of the latest advancements in the use of micropatterns for cell behavior regulation. It discusses the influence of micropattern morphology and coating on cell behavior and the underlying mechanisms. It also highlights future research directions in this field, aiming to inspire new investigations in materials medicine, regenerative medicine, and tissue engineering. The review underscores the potential of micropatterns as a novel approach for controlling cell behavior, which could pave the way for breakthroughs in various biomedical applications.
{"title":"Advances in Regulating Cellular Behavior Using Micropatterns.","authors":"Yizhou Li, Wenli Jiang, Xintong Zhou, Yicen Long, Yujia Sun, Ye Zeng, Xinghong Yao","doi":"10.59249/UXOH1740","DOIUrl":"10.59249/UXOH1740","url":null,"abstract":"<p><p>Micropatterns, characterized as distinct physical microstructures or chemical adhesion matrices on substance surfaces, have emerged as a powerful tool for manipulating cellular activity. By creating specific extracellular matrix microenvironments, micropatterns can influence various cell behaviors, including orientation, proliferation, migration, and differentiation. This review provides a comprehensive overview of the latest advancements in the use of micropatterns for cell behavior regulation. It discusses the influence of micropattern morphology and coating on cell behavior and the underlying mechanisms. It also highlights future research directions in this field, aiming to inspire new investigations in materials medicine, regenerative medicine, and tissue engineering. The review underscores the potential of micropatterns as a novel approach for controlling cell behavior, which could pave the way for breakthroughs in various biomedical applications.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"527-547"},"PeriodicalIF":2.7,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29eCollection Date: 2023-12-01DOI: 10.59249/AXGU7370
Bryan McDonald, Brent Y Chick, Diana C Hargreaves, Susan M Kaech
T cells undergo extensive chromatin remodeling over several days following stimulation through the T cell receptor. However, the kinetics and gene loci targeted by early remodeling events within the first 24 hours of T cell priming to orchestrate effector differentiation have not been well described. We identified that chromatin accessibility is rapidly and extensively remodeled within 1 hour of stimulation of naïve CD8+ T cells, leading to increased global chromatin accessibility at many effector T cell-associated genes that are enriched for AP-1, early growth response (EGR), and nuclear factor of activated T cells (NFAT) binding sites, but this short duration of stimulation is insufficient for commitment to clonal expansion in vivo. Sustained 24-hour stimulation led to further chromatin remodeling and was sufficient to enable clonal expansion. These data suggest that the duration of antigen receptor signaling is intimately coupled to chromatin remodeling and activation of genes involved in effector cell differentiation and highlight a potential mechanism that helps CD8+ T cells discriminate between foreign- and self-antigens.
T 细胞在受到 T 细胞受体刺激后的数天内会发生广泛的染色质重塑。然而,关于 T 细胞启动后 24 小时内早期重塑事件的动力学和目标基因位点以协调效应物分化的情况还没有很好的描述。我们发现,在刺激幼稚 CD8+ T 细胞的 1 小时内,染色质可及性被迅速、广泛地重塑,导致许多效应 T 细胞相关基因的全局染色质可及性增加,这些基因富含 AP-1、早期生长应答(EGR)和活化 T 细胞核因子(NFAT)结合位点,但这种短时间的刺激不足以导致体内克隆扩增。持续 24 小时的刺激会导致染色质进一步重塑,并足以实现克隆扩增。这些数据表明,抗原受体信号转导的持续时间与染色质重塑和效应细胞分化相关基因的激活密切相关,并强调了一种帮助 CD8+ T 细胞区分外来抗原和自身抗原的潜在机制。
{"title":"Early Chromatin Remodeling Events in Acutely Stimulated CD8<sup>+</sup> T Cells.","authors":"Bryan McDonald, Brent Y Chick, Diana C Hargreaves, Susan M Kaech","doi":"10.59249/AXGU7370","DOIUrl":"10.59249/AXGU7370","url":null,"abstract":"<p><p>T cells undergo extensive chromatin remodeling over several days following stimulation through the T cell receptor. However, the kinetics and gene loci targeted by early remodeling events within the first 24 hours of T cell priming to orchestrate effector differentiation have not been well described. We identified that chromatin accessibility is rapidly and extensively remodeled within 1 hour of stimulation of naïve CD8<sup>+</sup> T cells, leading to increased global chromatin accessibility at many effector T cell-associated genes that are enriched for AP-1, early growth response (EGR), and nuclear factor of activated T cells (NFAT) binding sites, but this short duration of stimulation is insufficient for commitment to clonal expansion <i>in vivo</i>. Sustained 24-hour stimulation led to further chromatin remodeling and was sufficient to enable clonal expansion. These data suggest that the duration of antigen receptor signaling is intimately coupled to chromatin remodeling and activation of genes involved in effector cell differentiation and highlight a potential mechanism that helps CD8<sup>+</sup> T cells discriminate between foreign- and self-antigens.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"467-473"},"PeriodicalIF":2.5,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-29eCollection Date: 2023-12-01DOI: 10.59249/FOSI4358
Savana Biondic, Sophie Petropoulos
Proper formation of the blastocyst, including the specification of the first embryonic cellular lineages, is required to ensure healthy embryo development and can significantly impact the success of assisted reproductive technologies (ARTs). However, the regulatory role of microRNAs in early development, particularly in the context of preimplantation lineage specification, remains largely unknown. Taking a cross-species approach, this review aims to summarize the expression dynamics and functional significance of microRNAs in the differentiation and maintenance of lineage identity in both the mouse and the human. Findings are consolidated from studies conducted using in vitro embryonic stem cell models representing the epiblast, trophectoderm, and primitive endoderm lineages (modeled by naïve embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm stem cells, respectively) to provide insight on what may be occurring in the embryo. Additionally, studies directly conducted in both mouse and human embryos are discussed, emphasizing similarities to the stem cell models and the gaps in our understanding, which will hopefully lead to further investigation of these areas. By unraveling the intricate mechanisms by which microRNAs regulate the specification and maintenance of cellular lineages in the blastocyst, we can leverage this knowledge to further optimize stem cell-based models such as the blastoids, enhance embryo competence, and develop methods of non-invasive embryo selection, which can potentially increase the success rates of assisted reproductive technologies and improve the experiences of those receiving fertility treatments.
{"title":"Evidence for Functional Roles of MicroRNAs in Lineage Specification During Mouse and Human Preimplantation Development.","authors":"Savana Biondic, Sophie Petropoulos","doi":"10.59249/FOSI4358","DOIUrl":"10.59249/FOSI4358","url":null,"abstract":"<p><p>Proper formation of the blastocyst, including the specification of the first embryonic cellular lineages, is required to ensure healthy embryo development and can significantly impact the success of assisted reproductive technologies (ARTs). However, the regulatory role of microRNAs in early development, particularly in the context of preimplantation lineage specification, remains largely unknown. Taking a cross-species approach, this review aims to summarize the expression dynamics and functional significance of microRNAs in the differentiation and maintenance of lineage identity in both the mouse and the human. Findings are consolidated from studies conducted using <i>in vitro</i> embryonic stem cell models representing the epiblast, trophectoderm, and primitive endoderm lineages (modeled by naïve embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm stem cells, respectively) to provide insight on what may be occurring in the embryo. Additionally, studies directly conducted in both mouse and human embryos are discussed, emphasizing similarities to the stem cell models and the gaps in our understanding, which will hopefully lead to further investigation of these areas. By unraveling the intricate mechanisms by which microRNAs regulate the specification and maintenance of cellular lineages in the blastocyst, we can leverage this knowledge to further optimize stem cell-based models such as the blastoids, enhance embryo competence, and develop methods of non-invasive embryo selection, which can potentially increase the success rates of assisted reproductive technologies and improve the experiences of those receiving fertility treatments.</p>","PeriodicalId":48617,"journal":{"name":"Yale Journal of Biology and Medicine","volume":"96 4","pages":"481-494"},"PeriodicalIF":2.7,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10751869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139075609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}