IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.99150

Susmita Sarkar, Saurabh Gupta, Chiranjit Mahato, Dibyendu Das, Jagannath Mondal

{"title":"Elucidating ATP's role as solubilizer of biomolecular aggregate.","authors":"Susmita Sarkar, Saurabh Gupta, Chiranjit Mahato, Dibyendu Das, Jagannath Mondal","doi":"10.7554/eLife.99150","DOIUrl":"10.7554/eLife.99150","url":null,"abstract":"Proteins occurring in significantly high concentrations in cellular environments (over 100 mg/ml) and functioning in crowded cytoplasm, often face the prodigious challenges of aggregation which are the pathological hallmark of aging and are critically responsible for a wide spectrum of rising human diseases. Here, we combine a joint-venture of complementary wet-lab experiment and molecular simulation to discern the potential ability of adenosine triphosphate (ATP) as solubilizer of protein aggregates. We show that ATP prevents both condensation of aggregation-prone intrinsically disordered protein Aβ40 and promotes dissolution of preformed aggregates. Computer simulation links ATP's solubilizing role to its ability to modulate protein's structural plasticity by unwinding protein conformation. We show that ATP is positioned as a superior biological solubilizer of protein aggregates over traditional chemical hydrotropes, potentially holding promises in therapeutic interventions in protein-aggregation-related diseases. Going beyond its conventional activity as energy currency, the amphiphilic nature of ATP enables its protein-specific interaction that would enhance ATP's efficiency in cellular processes.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intraspecific predator interference promotes biodiversity in ecosystems. 种内捕食者的干扰促进了生态系统的生物多样性。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.93115

Ju Kang, Shijie Zhang, Yiyuan Niu, Fan Zhong, Xin Wang

引用次数: 0

PRR adjuvants restrain high stability peptides presentation on APCs. PRR 佐剂可抑制高稳定性肽在 APC 上的呈现。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-30 DOI: 10.7554/eLife.99173

Bin Li, Jin Zhang, Taojun He, Hanmei Yuan, Hui Wu, Peng Wang, Chao Wu

{"title":"PRR adjuvants restrain high stability peptides presentation on APCs.","authors":"Bin Li, Jin Zhang, Taojun He, Hanmei Yuan, Hui Wu, Peng Wang, Chao Wu","doi":"10.7554/eLife.99173","DOIUrl":"10.7554/eLife.99173","url":null,"abstract":"Adjuvants can affect APCs function and boost adaptive immune responses post-vaccination. However, whether they modulate the specificity of immune responses, particularly immunodominant epitope responses, and the mechanisms of regulating antigen processing and presentation remain poorly defined. Here, using overlapping synthetic peptides, we screened the dominant epitopes of Th1 responses in mice post-vaccination with different adjuvants and found that the adjuvants altered the antigen-specific CD4+ T-cell immunodominant epitope hierarchy. MHC-II immunopeptidomes demonstrated that the peptide repertoires presented by APCs were significantly altered by the adjuvants. Unexpectedly, no novel peptide presentation was detected after adjuvant treatment, whereas peptides with high binding stability for MHC-II presented in the control group were missing after adjuvant stimulation, particularly in the MPLA- and CpG-stimulated groups. The low-stability peptide present in the adjuvant groups effectively elicited robust T-cell responses and formed immune memory. Collectively, our results suggest that adjuvants (MPLA and CpG) inhibit high-stability peptide presentation instead of revealing cryptic epitopes, which may alter the specificity of CD4+ T-cell-dominant epitope responses. The capacity of adjuvants to modify peptide-MHC (pMHC) stability and antigen-specific T-cell immunodominant epitope responses has fundamental implications for the selection of suitable adjuvants in the vaccine design process and epitope vaccine development.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sub-cone visual resolution by active, adaptive sampling in the human foveola. 在人类眼窝中通过主动、自适应采样实现子视锥视觉分辨率。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-29 DOI: 10.7554/eLife.98648

Jenny L Witten, Veronika Lukyanova, Wolf M Harmening

引用次数: 0

Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression. 纵向转录变化显示，自然杀伤细胞介导的细胞毒性通路中的基因是导致 COVID-19 进展的关键因素。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-29 DOI: 10.7554/eLife.94242

Matias A Medina, Francisco Fuentes-Villalobos, Claudio Quevedo, Felipe Aguilera, Raul Riquelme, Maria Luisa Rioseco, Sebastian Barria, Yazmin Pinos, Mario Calvo, Ian Burbulis, Camila Kossack, Raymond A Alvarez, Jose Luis Garrido, Maria Ines Barria

{"title":"Longitudinal transcriptional changes reveal genes from the natural killer cell-mediated cytotoxicity pathway as critical players underlying COVID-19 progression.","authors":"Matias A Medina, Francisco Fuentes-Villalobos, Claudio Quevedo, Felipe Aguilera, Raul Riquelme, Maria Luisa Rioseco, Sebastian Barria, Yazmin Pinos, Mario Calvo, Ian Burbulis, Camila Kossack, Raymond A Alvarez, Jose Luis Garrido, Maria Ines Barria","doi":"10.7554/eLife.94242","DOIUrl":"10.7554/eLife.94242","url":null,"abstract":"Patients present a wide range of clinical severities in response severe acute respiratory syndrome coronavirus 2 infection, but the underlying molecular and cellular reasons why clinical outcomes vary so greatly within the population remains unknown. Here, we report that negative clinical outcomes in severely ill patients were associated with divergent RNA transcriptome profiles in peripheral immune cells compared with mild cases during the first weeks after disease onset. Protein-protein interaction analysis indicated that early-responding cytotoxic natural killer cells were associated with an effective clearance of the virus and a less severe outcome. This innate immune response was associated with the activation of select cytokine-cytokine receptor pathways and robust Th1/Th2 cell differentiation profiles. In contrast, severely ill patients exhibited a dysregulation between innate and adaptive responses affiliated with divergent Th1/Th2 profiles and negative outcomes. This knowledge forms the basis of clinical triage that may be used to preemptively detect high-risk patients before life-threatening outcomes ensue.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11521369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regional response to light illuminance across the human hypothalamus. 人类下丘脑对光照度的区域反应。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-28 DOI: 10.7554/eLife.96576

Islay Campbell, Roya Sharifpour, Jose Fermin Balda Aizpurua, Elise Beckers, Ilenia Paparella, Alexandre Berger, Ekaterina Koshmanova, Nasrin Mortazavi, John Read, Mikhail Zubkov, Puneet Talwar, Fabienne Collette, Siya Sherif, Christophe Phillips, Laurent Lamalle, Gilles Vandewalle

{"title":"Regional response to light illuminance across the human hypothalamus.","authors":"Islay Campbell, Roya Sharifpour, Jose Fermin Balda Aizpurua, Elise Beckers, Ilenia Paparella, Alexandre Berger, Ekaterina Koshmanova, Nasrin Mortazavi, John Read, Mikhail Zubkov, Puneet Talwar, Fabienne Collette, Siya Sherif, Christophe Phillips, Laurent Lamalle, Gilles Vandewalle","doi":"10.7554/eLife.96576","DOIUrl":"10.7554/eLife.96576","url":null,"abstract":"Light exerts multiple non-image-forming biological effects on physiology including the stimulation of alertness and cognition. However, the subcortical circuitry underlying the stimulating impact of light is not established in humans. We used 7 Tesla functional magnetic resonance imaging to assess the impact of variations in light illuminance on the regional activity of the hypothalamus while healthy young adults (N=26; 16 women; 24.3±2.9 y) were completing two auditory cognitive tasks. We find that, during both the executive and emotional tasks, higher illuminance triggered an activity increase over the posterior part of the hypothalamus, which includes part of the tuberomamillary nucleus and the posterior part of the lateral hypothalamus. In contrast, increasing illuminance evoked a decrease in activity over the anterior and ventral parts of the hypothalamus, encompassing notably the suprachiasmatic nucleus and another part of the tuberomammillary nucleus. Critically, the performance of the executive task was improved under higher illuminance and was negatively correlated with the activity of the posterior hypothalamus area. These findings reveal the distinct local dynamics of different hypothalamus regions that underlie the impact of light on cognition.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11517251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Growing microglia in the lab. 在实验室中培育小胶质细胞

IF 6.4 1区生物学

eLife Pub Date : 2024-10-28 DOI: 10.7554/eLife.103535

Jonathan M Levenson, Hio Tong Kam, Dong Feng Chen

引用次数: 0

Development of a Marmoset Apparatus for Automated Pulling to study cooperative behaviors. 开发狨猴自动牵引装置，研究合作行为。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-28 DOI: 10.7554/eLife.97088

Olivia C Meisner, Weikang Shi, Nicholas A Fagan, Joel Greenwood, Monika P Jadi, Anirvan S Nandy, Steve W C Chang

{"title":"Development of a Marmoset Apparatus for Automated Pulling to study cooperative behaviors.","authors":"Olivia C Meisner, Weikang Shi, Nicholas A Fagan, Joel Greenwood, Monika P Jadi, Anirvan S Nandy, Steve W C Chang","doi":"10.7554/eLife.97088","DOIUrl":"10.7554/eLife.97088","url":null,"abstract":"In recent years, the field of neuroscience has increasingly recognized the importance of studying animal behaviors in naturalistic environments to gain deeper insights into ethologically relevant behavioral processes and neural mechanisms. The common marmoset (Callithrix jacchus), due to its small size, prosocial nature, and genetic proximity to humans, has emerged as a pivotal model toward this effort. However, traditional research methodologies often fail to fully capture the nuances of marmoset social interactions and cooperative behaviors. To address this critical gap, we developed the Marmoset Apparatus for Automated Pulling (MarmoAAP), a novel behavioral apparatus designed for studying cooperative behaviors in common marmosets. MarmoAAP addresses the limitations of traditional behavioral research methods by enabling high-throughput, detailed behavior outputs that can be integrated with video and audio recordings, allowing for more nuanced and comprehensive analyses even in a naturalistic setting. We also highlight the flexibility of MarmoAAP in task parameter manipulation which accommodates a wide range of behaviors and individual animal capabilities. Furthermore, MarmoAAP provides a platform to perform investigations of neural activity underlying naturalistic social behaviors. MarmoAAP is a versatile and robust tool for advancing our understanding of primate behavior and related cognitive processes. This new apparatus bridges the gap between ethologically relevant animal behavior studies and neural investigations, paving the way for future research in cognitive and social neuroscience using marmosets as a model organism.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11517257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The T cell receptor β chain repertoire of tumor infiltrating lymphocytes improves neoantigen prediction and prioritization. 肿瘤浸润淋巴细胞的T细胞受体β链谱系可改进新抗原预测和优先排序。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-28 DOI: 10.7554/eLife.94658

Thi Mong Quynh Pham, Thanh Nhan Nguyen, Bui Que Tran Nguyen, Thi Phuong Diem Tran, Nguyen My Diem Pham, Hoang Thien Phuc Nguyen, Thi Kim Cuong Ho, Dinh Viet Linh Nguyen, Huu Thinh Nguyen, Duc Huy Tran, Thanh Sang Tran, Truong Vinh Ngoc Pham, Minh Triet Le, Thi Tuong Vy Nguyen, Minh-Duy Phan, Hoa Giang, Hoai-Nghia Nguyen, Le Son Tran

{"title":"The T cell receptor β chain repertoire of tumor infiltrating lymphocytes improves neoantigen prediction and prioritization.","authors":"Thi Mong Quynh Pham, Thanh Nhan Nguyen, Bui Que Tran Nguyen, Thi Phuong Diem Tran, Nguyen My Diem Pham, Hoang Thien Phuc Nguyen, Thi Kim Cuong Ho, Dinh Viet Linh Nguyen, Huu Thinh Nguyen, Duc Huy Tran, Thanh Sang Tran, Truong Vinh Ngoc Pham, Minh Triet Le, Thi Tuong Vy Nguyen, Minh-Duy Phan, Hoa Giang, Hoai-Nghia Nguyen, Le Son Tran","doi":"10.7554/eLife.94658","DOIUrl":"10.7554/eLife.94658","url":null,"abstract":"In the realm of cancer immunotherapy, the meticulous selection of neoantigens plays a fundamental role in enhancing personalized treatments. Traditionally, this selection process has heavily relied on predicting the binding of peptides to human leukocyte antigens (pHLA). Nevertheless, this approach often overlooks the dynamic interaction between tumor cells and the immune system. In response to this limitation, we have developed an innovative prediction algorithm rooted in machine learning, integrating T cell receptor β chain (TCRβ) profiling data from colorectal cancer (CRC) patients for a more precise neoantigen prioritization. TCRβ sequencing was conducted to profile the TCR repertoire of tumor-infiltrating lymphocytes (TILs) from 28 CRC patients. The data unveiled both intra-tumor and inter-patient heterogeneity in the TCRβ repertoires of CRC patients, likely resulting from the stochastic utilization of V and J segments in response to neoantigens. Our novel combined model integrates pHLA binding information with pHLA-TCR binding to prioritize neoantigens, resulting in heightened specificity and sensitivity compared to models using individual features alone. The efficacy of our proposed model was corroborated through ELISpot assays on long peptides, performed on four CRC patients. These assays demonstrated that neoantigen candidates prioritized by our combined model outperformed predictions made by the established tool NetMHCpan. This comprehensive assessment underscores the significance of integrating pHLA binding with pHLA-TCR binding analysis for more effective immunotherapeutic strategies.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11517254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function. 核受体核心抑制因子 1 控制着调节性 T 细胞亚群的分化和效应功能。

IF 6.4 1区生物学

eLife Pub Date : 2024-10-28 DOI: 10.7554/eLife.78738

Valentina Stolz, Rafael de Freitas E Silva, Ramona Rica, Ci Zhu, Teresa Preglej, Patricia Hamminger, Daniela Hainberger, Marlis Alteneder, Lena Müller, Monika Waldherr, Darina Waltenberger, Anastasiya Hladik, Benedikt Agerer, Michael Schuster, Tobias Frey, Thomas Krausgruber, Sylvia Knapp, Clarissa Campbell, Klaus Schmetterer, Michael Trauner, Andreas Bergthaler, Christoph Bock, Nicole Boucheron, Wilfried Ellmeier

{"title":"Nuclear receptor corepressor 1 controls regulatory T cell subset differentiation and effector function.","authors":"Valentina Stolz, Rafael de Freitas E Silva, Ramona Rica, Ci Zhu, Teresa Preglej, Patricia Hamminger, Daniela Hainberger, Marlis Alteneder, Lena Müller, Monika Waldherr, Darina Waltenberger, Anastasiya Hladik, Benedikt Agerer, Michael Schuster, Tobias Frey, Thomas Krausgruber, Sylvia Knapp, Clarissa Campbell, Klaus Schmetterer, Michael Trauner, Andreas Bergthaler, Christoph Bock, Nicole Boucheron, Wilfried Ellmeier","doi":"10.7554/eLife.78738","DOIUrl":"10.7554/eLife.78738","url":null,"abstract":"FOXP3+ regulatory T cells (Treg cells) are key for immune homeostasis. Here, we reveal that nuclear receptor corepressor 1 (NCOR1) controls naïve and effector Treg cell states. Upon NCOR1 deletion in T cells, effector Treg cell frequencies were elevated in mice and in in vitro-generated human Treg cells. NCOR1-deficient Treg cells failed to protect mice from severe weight loss and intestinal inflammation associated with CD4+ T cell transfer colitis, indicating impaired suppressive function. NCOR1 controls the transcriptional integrity of Treg cells, since effector gene signatures were already upregulated in naïve NCOR1-deficient Treg cells while effector NCOR1-deficient Treg cells failed to repress genes associated with naïve Treg cells. Moreover, genes related to cholesterol homeostasis including targets of liver X receptor (LXR) were dysregulated in NCOR1-deficient Treg cells. However, genetic ablation of LXRβ in T cells did not revert the effects of NCOR1 deficiency, indicating that NCOR1 controls naïve and effector Treg cell subset composition independent from its ability to repress LXRβ-induced gene expression. Thus, our study reveals that NCOR1 maintains naïve and effector Treg cell states via regulating their transcriptional integrity. We also reveal a critical role for this epigenetic regulator in supporting the suppressive functions of Treg cells in vivo.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11517256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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