检索结果-内蒙古大学图书馆

Rb analog Whi5 regulates G1 to S transition and cell size but not replicative lifespan in budding yeast

Translational Medicine of Aging 2019年 3卷 104-108页

作者： Crane, Matthew M. Tsuchiya, Mitsuhiro Blue, Ben W. Almazan, Jared D. Chen, Kenneth L. Duffy, Siobhan R. Golubeva, Alexandra Grimm, Annaiz M. Guard, Alison M. Hill, Shauna A. Huynh, Ellen Kelly, Ryan M. Kiflezghi, Michael Kim, Hyunsung D. Lee, Mitchell Lee, Ting-I. Li, Jiayi Nguyen, Bao M.G. Whalen, Riley M. Yeh, Feng Y. McCormick, Mark Kennedy, Brian K. Delaney, Joe R. Kaeberlein, Matt Department of Pathology University of Washington Seattle WA United States Department of Genome Sciences University of Washington Seattle WA United States Medical Scientist Training Program University of Washington Seattle WA United States Department of Biochemistry and Molecular Biology University of New Mexico Albuquerque NM United States Buck Institute for Research on Aging Novato CA United States Department of Biochemistry and Molecular Biology Medical University of South Carolina Charleston SC United States

An increase in cell size with age is a characteristic feature of replicative aging in budding yeast. Deletion of the gene encoding Whi5 results in shortened duration of G1 and reduced cell size, and has been previously suggested to increase replicative lifespan. Upon careful analysis of multiple independently derived haploid and homozygous diploid whi5Δ mutants, we find no effect on lifespan, but we do confirm the reduction in cell size. We suggest that instead of antagonizing lifespan, the elongated G1 phase of the cell cycle during aging may actually play an important role in allowing aged cells time to repair accumulating DNA damage. © 2019 The Authors

关键词： Cell cycle regulation Replicative aging Saccharomyces cerevisiae

来源：评论

学校读者我要写书评

暂无评论

Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells (vol 1, pg 100003, 2020)

引用

CELL REPORTS MEDICINE 2020年第5期1卷 100003-100003页

作者： Reighard, Seth D. Cranert, Stacey A. Rangel, Kelly M. Ali, Ayad Gyurova, Ivayla E. de la Cruz-Lynch, Arthur T. Tuazon, Jasmine A. Khodoun, Marat V. Kottyan, Leah C. Smith, David F. Brunner, Hermine I. Waggoner, Stephen N. Center for Autoimmune Genomics and Etiology Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA Medical Scientist Training Program University of Cincinnati College of Medicine Cincinnati OH 45267 USA Immunology Graduate Training Program University of Cincinnati College of Medicine Cincinnati OH 45267 USA Division of Developmental Biology Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA Pathobiology and Molecular Medicine Graduate Program University of Cincinnati College of Medicine Cincinnati OH 45267 USA Division of Immunology Allergy and Rheumatology Department of Medicine University of Cincinnati Medical Center Cincinnati OH 45267 USA Department of Research Cincinnati Veterans Affairs Medical Center Cincinnati OH 45220 USA Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH 45267 USA Division of Pediatric Otolaryngology - Head & Neck Surgery Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA Division of Pulmonary and Sleep Medicine Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA Department of Otolaryngology - Head & Neck Surgery University of Cincinnati College of Medicine Cincinnati OH 45267 USA Division of Rheumatology Cincinnati Children’s Hospital Medical Center Cincinnati OH 45229 USA

Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells. CAR-expressing human natural killer (NK) cells robustly and discriminately eliminated PD-1high follicular human T cells in vitro and in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1low T cell subsets, including regulatory T cells. These results establish a strategy for specific targeting of PD-1high T cells that can be advanced as a clinical tool for the selective depletion of pathogenic follicular T cells or other PD-1high target cells in certain disease states.

关键词： systemic lupus erythematosus rheumatoid arthritis Sjögren syndrome allergy cytotherapy cytotoxicity checkpoint PD-L1 NK-92

来源：评论

学校读者我要写书评

暂无评论

Publisher Correction: Multistate and functional protein design using RoseTTAFold sequence space diffusion

引用

Nature biotechnology 2024年 2024 Oct 7页

作者： Sidney Lyayuga Lisanza Jacob Merle Gershon Samuel W K Tipps Jeremiah Nelson Sims Lucas Arnoldt Samuel J Hendel Miriam K Simma Ge Liu Muna Yase Hongwei Wu Claire D Tharp Xinting Li Alex Kang Evans Brackenbrough Asim K Bera Stacey Gerben Bruce J Wittmann Andrew C McShan David Baker Department of Biochemistry University of Washington Seattle WA USA. Institute for Protein Design University of Washington Seattle WA USA. Graduate Program in Biological Physics Structure and Design University of Washington Seattle WA USA. Department of Molecular Engineering University of Washington Seattle WA USA. Molecular & Cellular Biology Medical Scientist Training Program University of Washington Seattle WA USA. Faculty of Engineering Sciences Heidelberg University Heidelberg Germany. School of Chemistry and Biochemistry Georgia Institute of Technology Atlanta GA USA. Office of the Chief Scientific Officer Microsoft Redmond WA USA. Department of Biochemistry University of Washington Seattle WA USA. dabaker@uw.edu. Institute for Protein Design University of Washington Seattle WA USA. dabaker@uw.edu. Howard Hughes Medical Institute University of Washington Seattle WA USA. dabaker@uw.edu.

来源：评论

学校读者我要写书评

暂无评论

An optimized protocol for single cell transcriptional profiling by combinatorial indexing

arXiv

引用

arXiv 2021年

作者： Martin, Beth K. Qiu, Chengxiang Nichols, Eva Phung, Melissa Green-Gladden, Rula Srivatsan, Sanjay Blecher-Gonen, Ronnie Beliveau, Brian J. Trapnell, Cole Cao, Junyue Shendure, Jay Department of Genome Sciences University of Washington SeattleWA United States Department of Biology Case Western Reserve University ClevelandOH United States Division of Hematology/Oncology Seattle Children's Hospital SeattleWA United States Medical Scientist Training Program University of Washington SeattleWA United States The Crown Genomics Institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine Weizmann Institute of Science Israel Laboratory of Single-Cell Genomics and Population Dynamics The Rockefeller University New YorkNY United States Brotman Baty Institute for Precision Medicine SeattleWA United States Allen Discovery Center for Cell Lineage Tracing SeattleWA United States Howard Hughes Medical Institute SeattleWA United States

Single cell combinatorial indexing RNA sequencing (sci-RNA-seq)1,2 is a powerful method for recovering gene expression data from an exponentially scalable number of individual cells or nuclei. However, sci-RNA-seq is a complex protocol that has historically exhibited variable performance on different tissues, as well as lower sensitivity than alternative methods. Here we report a simplified, optimized version of the three-level sci-RNA-seq protocol that is faster, higher yield, more robust, and more sensitive, than the original sci-RNA-seq3 protocol, with reagent costs on the order of 1 cent per cell or less. We showcase the optimized protocol via whole organism analysis of an E16.5 mouse embryo, profiling ~380,000 nuclei in a single experiment. Finally, we introduce a "tiny sci-*" protocol for experiments where input is extremely limited. © 2021, CC BY-NC-SA.

关键词： RNA

来源：评论

学校读者我要写书评

暂无评论

Skin Staphylococcus aureus detection and relationship to atopic dermatitis outcomes using culture and metagenomic sequencing

引用

Scientific reports 2025年第1期15卷 17606页

作者： Arya Dahal Wan Chi Chang Elisabet Johansson Brittany Grashel David Morgan Lindsey Williams Mindy Hammonds Seiya Sachdeva Dan Spagna Latha Satish Jocelyn M Biagini Lisa J Martin David B Haslam Nicholas J Ollberding Gurjit K Khurana Hershey Division of Asthma Research Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue MLC 7037 Cincinnati OH 45229 USA. Medical Scientist Training Program University of Cincinnati College of Medicine Cincinnati OH 45229 USA. Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH 45229 USA. Division of Human Genetics Cincinnati Children's Hospital Medical Center Cincinnati OH 45229 USA. Microbial Genomics and Metagenomics Laboratory Cincinnati Children's Hospital Medical Center Cincinnati OH 45229 USA. Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical Center Cincinnati OH 45229 USA. Division of Asthma Research Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue MLC 7037 Cincinnati OH 45229 USA. Hersg101@***. Department of Pediatrics University of Cincinnati College of Medicine Cincinnati OH 45229 USA. Hersg101@***.

Staphylococcus aureus (SA) skin colonization in pediatric atopic dermatitis (AD) increases risk for severe AD and development of other allergic diseases. Despite this, there is no consensus regarding the optimal method to detect SA. Studies comparing metagenomic shotgun sequencing (MSS) and culture-based methods in SA detection and relationships to AD outcomes are lacking. In the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort, we defined SA colonization categories by contact agar plate sampling/culture and skin tape sampling/MSS: double negative, sequencing only positive, contact plate only positive, and double positive (n = 759). We assessed AD severity, sensitization, total IgE, and atopic outcomes across categories. Culture missed 69% of samples detected by MSS and MSS missed 54% of samples detected by culture. The double positive group exhibited higher AD severity, sensitization load, and total serum IgE, and was more likely to develop allergic rhinitis (AR) compared to other groups. Detection of SA by MSS or culture missed over half of the SA detected by the other method. Importantly, detection via both methods correlated with increased AD severity, sensitization, total IgE, and AR. Thus, these methods are complementary and both may be necessary for comprehensive evaluation of SA and its clinical and biologic impact.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Exploring the differences in the tumor microenvironment and immuno-oncologic targets in pancreatic ductal adenocarcinomas (PDAC) according to KRAS mutational status

ESMO Gastrointestinal Oncology

引用

ESMO Gastrointestinal Oncology 2024年 4卷 100042-100042页

作者： Faber, E.B. Baca, Y. Xiu, J. Walker, P. Manji, G. Gholami, S. Saeed, A. Prakash, A. Botta, G.P. Sohal, D. Lenz, H.J. Shields, A.F. Nabhan, C. El-Deiry, W. Seeber, A. Chiu, V. Hwang, J. Lou, E. Division of Hematology Oncology and Transplantation Department of Medicine University of Minnesota Minneapolis Medical Scientist Training Program University of Minnesota Medical School Minneapolis Caris Life Sciences Phoenix Division of Hematology and Oncology Department of Medicine Columbia University Irving Medical Center New York Northwell Health New York Division of Hematology/Oncology Department of Medicine University of Pittsburgh Medical Center Pittsburgh Division of Oncology Department of Medicine University of California—San Diego Health La Jolla Department of Medicine University of Cincinnati Cincinnati Division of Medical Oncology Department of Medicine Keck School of Medicine at the University of Southern California Los Angeles Barbara Ann Karmanos Cancer Institute at Wayne State University Detroit Department of Pathology and Laboratory Medicine Warren Alpert Medical School at Brown University Providence USA Department of Hematology and Oncology Comprehensive Cancer Center Innsbruck Medical University of Innsbruck/Tirol Kliniken Innsbruck Austria Cedars-Sinai The Angeles Clinic and Research Institute Los Angeles USA

BackgroundThe majority of pancreatic ductal adenocarcinomas (PDACs) are driven by mutant (mt) KRAS. How mt KRAS and co-driver mutations affect the immune cell (IC) landscape of PDAC remains uncertain. Herein, we characterize the types of IC in the PDAC tumor microenvironment (TME) and the prevalence of immuno-oncologic (IO) biomarkers by genomic and transcriptomic analysis in the context of KRAS status. Materials and methods4142 PDAC and 3727 colorectal cancer (CRC) cases with KRAS mt were analyzed using next-generation DNA sequencing, immunohistochemistry, and whole-transcriptome RNA sequencing. Microsatellite instability and deficiency in mismatch repair (MSI-H/dMMR) and tumor mutational burden (TMB) were also assessed. ResultsWe found KRAS mt in 81% of PDAC, with the most common variant being G12D in PDAC, and fewer cases of KRAS mt were co-expressed with the predictive IO marker MSI-H/dMMR than KRAS-wild-type (wt). However, KRASG12D, KRASG12V, and KRASQ61 mutations had significantly lower TMB than KRAS wt tumors in PDAC. The IC environment of KRAS mt PDAC showed significant differences in nearly all IC types; a similar pattern was observed in CRC but was less pronounced. ConclusionsTherapeutic IO targets like programmed death-ligand 1 are enriched in pancreatic adenocarcinoma cases harboring specific targetable variants of KRAS mt PDAC. Better understanding of the TME could lead to tailored immunotherapeutic strategies to overcome these barriers in KRAS mt PDAC, possibly in combination with molecularly targeted treatment strategies.

关键词： pancreatic cancer pancreatic adenocarcinoma KRAS genomics tumor microenvironment

来源：评论

学校读者我要写书评

暂无评论

Distance Metrics for Gamma Distributions

arXiv

引用

arXiv 2018年

作者： McCrimmon, Colin M. Medical Scientist Training Program University of California IrvineCA United States

Here I present the analytic form of two common distance metrics, the symmetrised Kullback-Leibler Divergence and the Kolmogorov-Smirnov statistic, as well as an extension of the Kolmogorov-Smirnov statistic for comparing theoretical gamma distributions. In doing so, I also present the analytic solution to the intersection of two gamma distributions. Lastly, I provide examples that demonstrate the similarity between these distance metrics and their usefulness in describing the separability of gamma distributions. Copyright © 2018, The Authors. All rights reserved.

关键词： Computational complexity

来源：评论

学校读者我要写书评

暂无评论

Single-cell profiling of bone metastasis ecosystems from multiple cancer types reveals convergent and divergent mechanisms of bone colonization

Cell genomics

引用

Cell genomics 2025年 100888页

作者： Fengshuo Liu Yunfeng Ding Zhan Xu Xiaoxin Hao Tianhong Pan George Miles Siyue Wang Yi-Hsuan Wu Jun Liu Igor L Bado Weijie Zhang Ling Wu Yang Gao Liqun Yu David G Edwards Hilda L Chan Sergio Aguirre Michael Warren Dieffenbach Elina Chen Yichao Shen Dane Hoffman Luis Becerra Dominguez Charlotte Helena Rivas Xiang Chen Hai Wang Zbigniew Gugala Robert L Satcher Xiang H-F Zhang Lester and Sue Smith Breast Center Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA Dan L. Duncan Cancer Center Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA Department of Molecular and Cellular Biology Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA Graduate Program in Cancer and Cell Biology Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. Department of Molecular and Cellular Biology Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. Department of Orthopedic Oncology University of Texas MD Anderson Cancer Center Houston TX USA. Dan L. Duncan Cancer Center Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. Graduate Program in Immunology and Microbiology Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. Medical Scientist Training Program Baylor College of Medicine Houston TX 77030 USA. Graduate Program in Cancer and Cell Biology Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA Graduate Program in Integrative Molecular and Biomedical Sciences Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. Graduate Program in Development Disease Models and Therapeutics Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. College of Natural Sciences University of Texas at Austin 110 Inner Campus Drive Austin TX 78706 USA. Department of Orthopedic Surgery and Rehabilitation University of Texas Medical Branch Galveston TX USA. Department of Orthopedic Oncology University of Texas MD Anderson Cancer Center Houston TX USA. Electronic address: rlsatcher@***. McNair Medical Institute Baylor College of Medicine One Baylor Plaza Houston TX 77030 USA. Electronic address: xiangz@bcm.edu.

Bone is a common site for metastasis of solid cancers. The diversity of histological and molecular characteristics of bone metastases (BMs) remains poorly studied. Here, we performed single-cell RNA sequencing on 42 BMs from eight cancer types, identifying three distinct ecosystem archetypes, each characterized by an enrichment of specific immune cells: macrophages/osteoclasts, regulatory/exhausted T cells, or monocytes. We validated these archetypes by immunostaining on tissue sections and bioinformatic analysis of bulk RNA sequencing/microarray data from 158 BMs across more than 10 cancer types. Interestingly, we found only a modest correlation between the BM archetypes and the tissues of origin; BMs from the same cancer type often fell into different archetypes, while BMs from different cancer types sometimes converged on the same archetype. Additional analyses revealed parallel immunosuppression and bone remodeling mechanisms, some of which were experimentally validated. Overall, we discovered unappreciated heterogeneity of BMs across different cancers.

关键词： bone metastases convergent and divergent evolution immune archetypes immune evasion immunosuppression single-cell RNA sequencing tumor microenvironment

来源：评论

学校读者我要写书评

暂无评论

DIPG-58. Therapeutic HDAC targeting in hypermutant CNS tumors

引用

Neuro-Oncology 2022年第SUPPLEMENT_1期24卷 i32-i32页

作者： Myers, Carrie Noll, Alyssa Biery, Matthew Meechan, Michael Tahiri, Sophie Foster, Jessica Dun, Matthew Olson, James Vitanza, Nicholas The Ben Towne Center for Childhood Cancer Research Seattle Children’s Research Institute Seattle WA USA Molecular and Cellular Biology Graduate Program and Medical Scientist Training Program University of Washington Seattle Washington USA Division of Oncology The Children's Hospital of Philadelphia Philadelphia PA USA Department of Pediatrics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA Cancer Signaling Research Group School of Biomedical Sciences and Pharmacy College of Health Medicine and Wellbeing University of Newcastle Callaghan NSW Australia Individualised Medicine Program Hunter Medical Research Institute New Lambton Heights NSW Australia Division of Pediatric Hematology Oncology Bone Marrow Transplant and Cellular Therapy Department of Pediatrics Seattle Children’s Hospital University of Washington Seattle WA USA

Diffuse intrinsic pontine glioma (DIPG) is a universally fatal tumor of the pons, most often characterized by mutations in genes encoding histone 3, that led to the classification diffuse midline glioma, H3 K27M-mutant (DMG). However, 15% of DIPG are histone wildtype (H3WT) and can have a hypermutant phenotype, characterized by mutations in DNA mismatch repair that also occur in pediatric high-grade glioma (pHGG). We previously published the preclinical efficacy of quisinostat in DMG. As hypermutant CNS tumors share transcriptional disruption with DMG, we investigated if HDAC inhibition was also therapeutic against hypermutant DIPG and pHGG. We tested PBT-24, a PMS2 mutant, treatment-naïve, patient-derived hypermutant DIPG model, and found similar quisinostat sensitivity compared to other DMG cultures in vitro (IC50 = ~30 nM), as well as significant efficacy in a xenograft flank model (60 day mean tumor size of 1109mm3 [vehicle] vs. 19mm3 [quisinostat-treated]). This in vivo effect was greater than the anti-tumor effect observed in a xenograft flank non-hypermutant DMG model PBT-09 (60 day mean tumor size of 1006mm3 [vehicle] vs. 244mm3 [quisinostat-treated]). To validate the effect of hypermutation on sensitivity to quisinostat, we generated PMS2 knock-out (KO) and MSH2 KO isogenic cell lines using the H3WT model VUMC-DIPG-10. In a xenograft flank model, we observed increased quisinostat sensitivity in the KO models (20 day mean tumor volume of 547mm3 [parental], 396mm3 [PMS2 KO], and 150mm3 [MSH2 KO]). RNA sequencing of quisinostat-treated PBT-24 revealed an increase in acute inflammatory response genes which we are investigating as a mechanism of action for HDACi against hypermutant tumors. Ultimately, we demonstrate the in vivo efficacy of quisinostat against hypermutant DIPG that supports the investigation of HDAC inhibition as a treatment strategy across hypermutant CNS tumors.

关键词：

来源：评论

学校读者我要写书评

暂无评论

Author Correction: Light-based vat-polymerization bioprinting

Nature Reviews Methods Primers

引用

Nature Reviews Methods Primers 2024年第1期4卷 1页

作者： Riccardo Levato Oksana Dudaryeva Carlos Ezio Garciamendez-Mijares Yu Shrike Zhang Bruce E. Kirkpatrick Kristi S. Anseth Riccardo Rizzo Marcy Zenobi-Wong Jacob Schimelman Shaochen Chen Department of Clinical Sciences Faculty of Veterinary Medicine Utrecht University Utrecht Netherlands Department of Orthopedics University Medical Center Utrecht Utrecht Netherlands Division of Engineering in Medicine Brigham and Women’s Hospital Department of Medicine Harvard Medical School Cambridge MA USA Department of Chemical and Biological Engineering University of Colorado Boulder Boulder CO USA BioFrontiers Institute University of Colorado Boulder Boulder CO USA Medical Scientist Training Program University of Colorado Anschutz Medical Campus Aurora CO USA Department of Health Sciences and Technology ETH Zürich Zürich Switzerland Wyss Institute for Biologically Inspired Engineering Harvard University Boston MA USA Harvard John A. Paulson School of Engineering and Applied Sciences Harvard University Boston MA USA Department of NanoEngineering University of California San Diego La Jolla CA USA

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：