TRBC1-targeting antibody–drug conjugates for the treatment of T cell cancers
Nature
Published On 2024/4
Antibody and chimeric antigen receptor (CAR) T cell-mediated targeted therapies have improved survival in patients with solid and haematologic malignancies 1, 2, 3, 4, 5, 6, 7, 8, 9. Adults with T cell leukaemias and lymphomas, collectively called T cell cancers, have short survival 10, 11 and lack such targeted therapies. Thus, T cell cancers particularly warrant the development of CAR T cells and antibodies to improve patient outcomes. Preclinical studies showed that targeting T cell receptor β-chain constant region 1 (TRBC1) can kill cancerous T cells while preserving sufficient healthy T cells to maintain immunity 12, making TRBC1 an attractive target to treat T cell cancers. However, the first-in-human clinical trial of anti-TRBC1 CAR T cells reported a low response rate and unexplained loss of anti-TRBC1 CAR T cells 13, 14. Here we demonstrate that CAR T cells are lost due to killing by the patient’s normal T …
Journal
Nature
Published On
2024/4
Volume
628
Issue
8,007
Page
416-423
Authors
Bert Vogelstein
Johns Hopkins University
Position
H-Index(all)
289
H-Index(since 2020)
144
I-10 Index(all)
0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
Cited By
0
Research Interests
Cancer
Biology
University Profile Page
Kenneth Kinzler
Johns Hopkins University
Position
H-Index(all)
248
H-Index(since 2020)
136
I-10 Index(all)
0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
Cited By
0
Research Interests
Cancer
Genetics
Genomics
University Profile Page
Andrew Pardoll
Johns Hopkins University
Position
school of medicine
H-Index(all)
168
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111
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0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
Cited By
0
Research Interests
immunology
cancer
immunotheapy
University Profile Page
Chetan Bettegowda
Johns Hopkins University
Position
Jennison and Novak Families Professor Department of Neurosurgery
H-Index(all)
59
H-Index(since 2020)
50
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0
I-10 Index(since 2020)
0
Citation(all)
0
Citation(since 2020)
0
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0
Research Interests
Cancer genetics
Neurosurgery
Neuro-oncology
University Profile Page
Nina Wagner-Johnston
Johns Hopkins University
Position
Associate Professor
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53
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43
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0
I-10 Index(since 2020)
0
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0
Citation(since 2020)
0
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0
Research Interests
oncology
lymphoma
University Profile Page
Maximilian F. Konig
Johns Hopkins University
Position
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24
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23
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0
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0
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0
Citation(since 2020)
0
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0
Research Interests
Rheumatology
Immuno-oncology
Precision immunotherapy
T cell engineering
University Profile Page
Stephanie Glavaris
Johns Hopkins University
Position
Research Specialist
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15
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14
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0
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0
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0
Citation(since 2020)
0
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0
Research Interests
Cancer
Biology
University Profile Page
Suman Paul
Johns Hopkins University
Position
Medical Oncology Fellow & Hospital
H-Index(all)
14
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12
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0
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0
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0
Citation(since 2020)
0
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0
Research Interests
Hematology
Oncology
Immunology
Cell Biology
University Profile Page
Other Articles from authors
Chetan Bettegowda
Johns Hopkins University
World neurosurgery
Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma
ObjectiveCareful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics.MethodsRetrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with …
2024/2/1
Article DetailsChetan Bettegowda
Johns Hopkins University
Journal of Neuro-Oncology
Exploring the impact of primary care utilization and health information exchange upon treatment patterns and clinical outcomes of glioblastoma patients
PurposeThere is limited literature describing care coordination for patients with glioblastoma (GBM). We aimed to investigate the impact of primary care and electronic health information exchange (HIE) between neurosurgeons, oncologists, and primary care providers (PCP) on GBM treatment patterns, postoperative outcomes, and survival.MethodsWe identified adult GBM patients undergoing primary resection at our institution (2007–2020). HIE was defined as shared electronic medical information between PCPs, oncologists, and neurosurgeons. Multivariate logistic regression analyses were used to determine the effect of PCPs and HIE upon initiation and completion of adjuvant therapy. Kaplan-Meier and multivariate Cox regression models were used to evaluate overall survival (OS).ResultsAmong 374 patients (mean age±SD: 57.7±13.5, 39.0% female), 81.0% had a PCP and 62.4% had electronic HIE. In …
2024/4/25
Article DetailsKenneth Kinzler
Johns Hopkins University
Science Translational Medicine
Machine learning to detect the SINEs of cancer
We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the …
2024/1/24
Article DetailsBert Vogelstein
Johns Hopkins University
Circulating mutant dna to assess tumor dynamics
DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. We apply a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in body samples of patients. Measurements of ctDNA can be used to reliably monitor tumor dynamics in subjects with cancer, especially those who are undergoing surgery or chemotherapy. This personalized genetic approach can be generally applied.
2024/1/4
Article DetailsNina Wagner-Johnston
Johns Hopkins University
Blood Advances
Myeloablative Versus Non-Myeloablative Consolidation for Primary Central Nervous System Lymphoma: Results of Alliance 51101
While it is evident that standard dose whole brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the U.S. Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with non-myeloablative consolidation after induction therapy for PCNSL. This is the first randomized trial to be initiated that eliminates whole brain radiotherapy as a consolidative approach in newly-diagnosed PCNSL. Patients, age 18-75 years, were randomly assigned in a 1:1 manner to induction therapy (methotrexate, temozolomide, rituximab and cytarabine) followed by consolidation with either thiotepa plus carmustine and autologous stem cell rescue versus induction followed by non-myeloablative …
2024/4/12
Article DetailsChetan Bettegowda
Johns Hopkins University
World neurosurgery
The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas
ObjectiveIntramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Anticipating a subependymoma on preoperative imaging can inform surgical decision-making and improve patient counseling. Here, we present our experience recognizing IMSC subependymomas on preoperative magnetic resonance imaging (MRI) based on a distinctive characteristic termed the “ribbon sign.”MethodsWe retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The “ribbon sign” was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense …
2023/7/1
Article DetailsAndrew Pardoll
Johns Hopkins University
Journal of translational medicine
Comparing anti-tumor and anti-self immunity in a patient with melanoma receiving immune checkpoint blockade
BackgroundTumor regression following immune checkpoint blockade (ICB) is often associated with immune-related adverse events (irAEs), marked by inflammation in non-cancerous tissues. This study was undertaken to investigate the functional relationship between anti-tumor and anti-self immunity, to facilitate irAE management while promoting anti-tumor immunity.MethodsMultiple biopsies from tumor and inflamed tissues were collected from a patient with melanoma experiencing both tumor regression and irAEs on ICB, who underwent rapid autopsy. Immune cells infiltrating melanoma lesions and inflamed normal tissues were subjected to gene expression profiling with multiplex qRT-PCR for 122 candidate genes. Subsequently, immunohistochemistry was conducted to assess the expression of 14 candidate markers of immune cell subsets and checkpoints. TCR-beta sequencing was used to explore T cell …
2024/3/5
Article DetailsMaximilian F. Konig
Johns Hopkins University
ACR Open Rheumatology
Clinical Images: Frosted branch angiitis in systemic lupus erythematosus
A 28-year-old woman with history of systemic lupus erythematosus (SLE) since 2014 with previous involvement including arthritis, myositis, and cutaneous small vessel vasculitis, presented with two weeks of fever and rash. There were (A) 10 cm–diameter bullae on bilateral feet dorsa and vesicles on her elbows. White blood cell count was 13,900 cells/mm3, hemoglobin was 13.4 g/dL, and platelets were 317,000 cells/mm3. Erythrocyte sedimentation rate and C-reactive protein were elevated. Renal function and complement levels were normal. Anti-RNP IgG was> 644, anti-Sm IgG was 333 (reference range< 20). Antineutrophilic cytoplasmic antibody (ANCA), rheumatoid factor, cryoglobulins, and antiphospholipid antibodies were negative. Lupus anticoagulant was positive. She developed severe sequential vision loss during hospitalization.(B) Fundoscopy and (C) retinal imaging showed bilateral diffuse vascular …
2024/4
Article DetailsBert Vogelstein
Johns Hopkins University
Methods of detecting high risk barrett's esophagus with dysplasia, and esophageal adenocarcinoma
AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O ([C@ H] 1C [C@@](O)(CC= 2C (O)= C3C (= O) C= 4C= CC= C (C= 4C (= O) C3= C (O) C= 21) OC) C (= O) CO)[C@ H] 1C [C@ H](N)[C@@ H](O)[C@ H](C) O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 6GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1= C (F) C (NC (= O) OCCCCC)= NC (= O) N1 [C@ H] 1 [C@ H](O)[C@ H](O)[C@@ H](C) O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 6
2024/2/29
Article DetailsAndrew Pardoll
Johns Hopkins University
OncoImmunology
CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy
Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and …
2024/12/31
Article DetailsChetan Bettegowda
Johns Hopkins University
Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials
IntroductionNeurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies.MethodsThe Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings.ResultsLiquid biopsy has emerged as a promising assay for neurofibromatosis 1 …
2024/2
Article DetailsChetan Bettegowda
Johns Hopkins University
Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: a RANO review
Background The utility of liquid biopsies is well documented in several extracranial and intracranial (brain/leptomeningeal metastases, gliomas) tumors. Methods The RANO (Response Assessment in Neuro-Oncology) group has set up a multidisciplinary Task Force to critically review the role of blood and CSF-liquid biopsy in central nervous system lymphomas, with a main focus on primary central nervous system lymphomas (PCNSL). Results Several clinical applications are suggested: diagnosis of PCNSL in critical settings (elderly or frail patients, deep locations, steroids responsiveness), definition of minimal residual disease, early indication of tumor response or relapse following treatments and prediction of outcome. Conclusions Thus far, no clinically validated circulating biomarkers for managing both primary and secondary CNS …
2024/4/10
Article DetailsChetan Bettegowda
Johns Hopkins University
Neurosurgery
380 2021 WHO Grading Scheme Provides Minimal Incremental Improvement in Prognostic Stratification of a Retrospective IDH-Mutant Astrocytoma Cohort Compared to 2016 WHO Grading …
METHODS:We retrospectively identified 176 adult IDHmAstro patients with available next-generation sequencing (NGS). All tumors were regraded based on the 2021 and 2016 WHO grading schema using relevant histopathological (mitotic rate, microvascular proliferation, necrosis) and molecular (CDKN2A) features. The prognostic ability of each grading schema was evaluated with Kaplan-Meier and multivariate Cox Regression analyses.RESULTS:The cohort consisted of 76 grade 2 (43.2%), 45 grade 3 (25.6%), and 55 grade 4 (31.3%) IDHmAstro cases using the 2021 grading schema. Only four patients (2%) had a grade change from the 2016 WHO grading scheme-one prior 2016 WHO grade II and three grade III tumors, all regraded to Grade 4 based on present CDKN2A homozygous deletion. When assessed based on both classification schemas, WHO Grade 4/IV tumors were associated with lower OS than …
2024/4/1
Article DetailsChetan Bettegowda
Johns Hopkins University
Characterizing the presentation, management, and clinical outcomes of patients with intradural spinal chordomas: a systematic review
OBJECTIVE Chordomas are locally aggressive neoplasms of the spine or skull base that arise from embryonic remnants of the notochord. Intradural chordomas represent a rare subset of these neoplasms, and few studies have described intradural chordomas in the spine. This review evaluates the presentation, management, and outcomes of intradural spinal chordomas. METHODS A systematic review of PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science was performed. Studies describing at least 1 case of intradural chordomas anywhere in the spine were included. Extracted details included presenting symptoms, radiological findings, treatment course, follow-up, and disease progression. RESULTS Thirty-one studies, with a total of 41 patients, were included in this review. Seventy-six percent (31/41) of patients had …
2024/5/1
Article DetailsKenneth Kinzler
Johns Hopkins University
Circulating tumor DNA analysis informing adjuvant chemotherapy in locally advanced rectal cancer: The randomized AGITG DYNAMIC-Rectal study.
12Background: Adjuvant chemotherapy (CT) following neoadjuvant chemoradiation and surgery for locally advanced rectal cancer (LARC) is widely adopted, despite uncertain survival benefit. Circulating tumor DNA (ctDNA) detection after surgery has been shown to be a strong prognostic marker in localized colorectal cancer and potentially could inform adjuvant treatment decision making. Methods: AGITG DYNAMIC-Rectal is a multi-centre randomized controlled phase II trial. Eligible patients (pts) had LARC (cT3-4 and/or cN+) treated with neoadjuvant chemoradiation, total mesorectal excision, and were fit for adjuvant CT. Pts were randomly assigned 2:1 to ctDNA-guided management or standard management (clinician decision). A tumor-informed personalized ctDNA assay was used. For the ctDNA-guided group, a positive result at 4 and/or 7 weeks after surgery prompted 4 months of oxaliplatin-based or …
2024/1/20
Article DetailsKenneth Kinzler
Johns Hopkins University
Safe sequencing system
The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called “Safe-SeqS” for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule;(ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant (“super-mutants”) if≥ 95% of them contain the identical mutation. We illustrate the …
2023/10/3
Article DetailsChetan Bettegowda
Johns Hopkins University
Journal of Neurosurgery: Spine
Exploring disparities in surgical recommendations for patients with primary intramedullary spinal cord tumors: an analysis of the Surveillance, Epidemiology, and End Results …
OBJECTIVE Factors that may drive recommendations for operative intervention for patients with intramedullary spinal cord tumors (ISCTs) have yet to be extensively studied. The authors investigated racial and socioeconomic disparities in the management of patients with primary spinal cord ependymomas and nonependymal gliomas, with the aim of determining the associations between socioeconomic patient characteristics, survival, and recommendations for the resection of primary ISCTs. METHODS The Surveillance, Epidemiology, and End Results registry was queried to identify all patients> 18 years of age with ISCTs diagnosed between 2000 and 2019. Univariable and multivariable logistic regression analyses were used to calculate odds ratios for variables associated with receiving a surgical recommendation. Log-rank tests and multivariable Cox proportional hazards models were used to investigate …
2024/3/22
Article DetailsNina Wagner-Johnston
Johns Hopkins University
Journal of the National Comprehensive Cancer Network
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent’s toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of …
2024/4/1
Article DetailsOther articles from Nature journal
Shiro Maeda
University of the Ryukyus
Nature
Genetic drivers of heterogeneity in type 2 diabetes pathophysiology
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes, and molecular mechanisms that are often specific to cell type,. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10−8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster …
2024/2/19
Article DetailsMichal Pyzik
Harvard University
Nature
Author Correction: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion
Author Correction: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion Author Correction: CEACAM1 regulates TIM-3-mediated tolerance and exhaustion Nature. 2024 Feb 9. doi: 10.1038/s41586-024-07164-y. Online ahead of print. Authors Yu-Hwa Huang 1 , Chen Zhu # 2 , Yasuyuki Kondo # 1 , Ana C Anderson 2 , Amit Gandhi 1 , Andrew Russell 3 , Stephanie K Dougan 4 , Britt-Sabina Petersen 5 , Espen Melum 1 6 , Thomas Pertel 2 , Kiera L Clayton 7 , Monika Raab 8 , Qiang Chen 9 , Nicole Beauchemin 10 , Paul J Yazaki 11 , Michal Pyzik 1 , Mario A Ostrowski 7 12 , Jonathan N Glickman 13 , Christopher E Rudd 8 , Hidde L Ploegh 4 , Andre Franke 5 , Gregory A Petsko 3 , Vijay K Kuchroo 2 , Richard S Blumberg 14 Affiliations 1 Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, 02115, Massachusetts, USA. 2 …
2024/2/9
Article DetailsMichal Pyzik
Harvard University
Nature
CEACAM1 regulates TIM-3-mediated tolerance and exhaustion
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2016
Article DetailsMark Maslin
University College London
Nature
Why it was right to reject the Anthropocene as a geological epoch
EconPapers: Why it was right to reject the Anthropocene as a geological epoch EconPapers Economics at your fingertips EconPapers Home About EconPapers Working Papers Journal Articles Books and Chapters Software Components Authors JEL codes New Economics Papers Advanced Search EconPapers FAQ Archive maintainers FAQ Cookies at EconPapers Format for printing The RePEc blog The RePEc plagiarism page Why it was right to reject the Anthropocene as a geological epoch Mark Maslin (), Matthew Edgeworth, Erle C. Ellis and Philip L. Gibbard Nature, 2024, vol. 629, issue 8010, 41-41 Abstract: Letter to the Editor Keywords: Geology; Environmental sciences; Climate change; Sustainability (search for similar items in EconPapers) Date: 2024 References: Add references at CitEc Citations: Downloads: (external link) https://www.nature.com/articles/d41586-024-01268-1 Abstract (text/html) Access to …
2024
Article DetailsSusan G. W. Laurance
James Cook University
Nature
Consistent patterns of common species across tropical tree communities
Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations, , , , – in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite …
2024/1/10
Article DetailsGuilherme M. Antar
Universidade de São Paulo
Nature
Phylogenomics and the rise of the angiosperms
Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods,. A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome,. Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins, –. However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes. This 15-fold increase in genus-level sampling relative to comparable nuclear studies provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating …
2024/4/24
Article DetailsIzaac Mitchell
Ulsan National Institute of Science and Technology
Nature
Graphene nanoribbons grown in hBN stacks for high-performance electronics
Van der Waals encapsulation of two-dimensional materials in hexagonal boron nitride (hBN) stacks is a promising way to create ultrahigh-performance electronic devices 1, 2, 3, 4. However, contemporary approaches for achieving van der Waals encapsulation, which involve artificial layer stacking using mechanical transfer techniques, are difficult to control, prone to contamination and unscalable. Here we report the transfer-free direct growth of high-quality graphene nanoribbons (GNRs) in hBN stacks. The as-grown embedded GNRs exhibit highly desirable features being ultralong (up to 0.25 mm), ultranarrow (< 5 nm) and homochiral with zigzag edges. Our atomistic simulations show that the mechanism underlying the embedded growth involves ultralow GNR friction when sliding between AA′-stacked hBN layers. Using the grown structures, we demonstrate the transfer-free fabrication of embedded GNR field …
2024/4
Article DetailsDean Mobbs PhD
California Institute of Technology
Nature
A synthesis of evidence for policy from behavioural science during COVID-19
Scientific evidence regularly guides policy decisions, with behavioural science increasingly part of this process. In April 2020, an influential paper proposed 19 policy recommendations (‘claims’) detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to …
2024/1/4
Article DetailsMaksim Litskevich
Princeton University
Nature
A hybrid topological quantum state in an elemental solid
Topology, – and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a ‘hybrid’ topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a …
2024/4/10
Article DetailsProf. Sahra Talamo
Università degli Studi di Bologna
Nature
Homo sapiens reached the higher latitudes of Europe by 45,000 years ago
The Middle to Upper Palaeolithic transition in Europe is associated with the regional disappearance of Neanderthals and the spread of Homo sapiens. Late Neanderthals persisted in western Europe several millennia after the occurrence of H. sapiens in eastern Europe1. Local hybridization between the two groups occurred2, but not on all occasions3. Archaeological evidence also indicates the presence of several technocomplexes during this transition, complicating our understanding and the association of behavioural adaptations with specific hominin groups4. One such technocomplex for which the makers are unknown is the Lincombian–Ranisian–Jerzmanowician (LRJ), which has been described in northwestern and central Europe5–8. Here we present the morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains directly associated …
2024/1/31
Article DetailsPing-Chieh Pao
Massachusetts Institute of Technology
Nature
Multisensory gamma stimulation promotes glymphatic clearance of amyloid
The glymphatic movement of fluid through the brain removes metabolic waste, , –. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer’s disease, , –. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer’s disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings …
2024/2/28
Article DetailsAshot Margaryan
Københavns Universitet
Nature
Population genomics of post-glacial western Eurasia
Western Eurasia witnessed several large-scale human migrations during the Holocene, , , –. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness …
2024/1/11
Article DetailsClary Clish
Harvard University
Nature
Reverse metabolomics for the discovery of chemical structures from humans
Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis,, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn’s disease. Several of these compounds and …
2024/2/8
Article DetailsMingyao Li
University of Pennsylvania
Nature
An atlas of epithelial cell states and plasticity in lung adenocarcinoma
Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival …
2024/2/28
Article DetailsEsther García-Domínguez
Universidad de Valencia
Nature
Multimodal cell atlas of the ageing human skeletal muscle
Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples,. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic …
2024/4/22
Article DetailsDeborah Doroshow
Yale University
Nature
An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis
Myeloid cells are known to suppress antitumour immunity. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells …
2024/1/4
Article DetailsGuofan Shao
Purdue University
Nature
Urban trees: how to maximize their benefits for humans and the environment
EconPapers: Urban trees: how to maximize their benefits for humans and the environment EconPapers Economics at your fingertips EconPapers Home About EconPapers Working Papers Journal Articles Books and Chapters Software Components Authors JEL codes New Economics Papers Advanced Search EconPapers FAQ Archive maintainers FAQ Cookies at EconPapers Format for printing The RePEc blog The RePEc plagiarism page Urban trees: how to maximize their benefits for humans and the environment Lina Tang (), Guofan Shao and Peter M. Groffman Nature, 2024, vol. 626, issue 7998, 261-261 Abstract: Letter to the Editor Keywords: Policy; Sustainability; Environmental sciences (search for similar items in EconPapers) Date: 2024 References: Add references at CitEc Citations: Track citations by RSS feed Downloads: (external link) https://www.nature.com/articles/d41586-024-00300-8 Abstract (text/…
2024
Article DetailsBenjamin Z. Houlton
Cornell University
Nature
Fertilizer management for global ammonia emission reduction
Crop production is a large source of atmospheric ammonia (NH 3), which poses risks to air quality, human health and ecosystems 1, 2, 3, 4, 5. However, estimating global NH 3 emissions from croplands is subject to uncertainties because of data limitations, thereby limiting the accurate identification of mitigation options and efficacy 4, 5. Here we develop a machine learning model for generating crop-specific and spatially explicit NH 3 emission factors globally (5-arcmin resolution) based on a compiled dataset of field observations. We show that global NH 3 emissions from rice, wheat and maize fields in 2018 were 4.3±1.0 Tg N yr− 1, lower than previous estimates that did not fully consider fertilizer management practices 6, 7, 8, 9. Furthermore, spatially optimizing fertilizer management, as guided by the machine learning model, has the potential to reduce the NH 3 emissions by about 38%(1.6±0.4 Tg N yr− 1 …
2024/2
Article DetailsBenjamin Z. Houlton
Cornell University
Nature
Reply to: Model uncertainty obscures major driver of soil carbon
Understanding the formation and stabilization mechanisms of soil organic carbon (SOC) is important for managing land carbon (C) and mitigating climate change. Tao et al. 1 reported that microbial C use efficiency (CUE) is the primary determinant of global SOC storage and that the relative impact of plant C inputs on SOC is minor. Although soil microbes undoubtedly play an important role in SOC cycling, we are concerned about the robustness of the approach taken by Tao et al. 1. The potential biases in their analyses may lead to misleading, model-dependent results.An important piece of evidence in support of an empirical relationship between CUE and SOC stems from a meta-analysis based on 132 paired CUE and SOC measurements. Tao et al. 1 applied a linear mixed-effects model to this dataset that included CUE, mean annual temperature (MAT), soil depth and random effects and explained 55% of the …
2024/3/7
Article DetailsPatricia Rios Mendoza
Universidad Autónoma de Madrid
Nature
Population genomics of post-glacial western Eurasia
Western Eurasia witnessed several large-scale human migrations during the Holocene, , , –. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness …
2024/1/11
Article Details