source_doi stringlengths 13 57 | source_mag_paper_id int64 490k 157M | source_abstract stringlengths 8 10.7k | target_doi stringlengths 14 27 | target_summary stringlengths 42 889 |
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10.1126/scisignal.2002299 | 17,935,792 | A signaling complex enables the compartmentalized regulation of cyclic AMP signaling by calcium entering through a specific channel. | 10.1038/s41577-018-0110-7 | This is an article identifying the physical interaction between ORAI1 and adenylyl cyclase 8 as a determinant for Ca 2+ and cAMP signalling crosstalk |
10.1126/science.abf3002 | 134,915,139 | Mom’s IL-6 rewires baby’s gut immunity Most infections that occur during pregnancy are mild and transient. However, whether such pathogen encounters can shape the long-term trajectory of the offspring’s immune system remains unclear. Lim et al . infected pregnant mice with the common food-borne pathogen Yersinia pseudo... | 10.1038/s41586-022-04919-3 | This study identifies intergenerational memory in intestinal offspring epithelial stem cells following in utero esposure to inflammatory mediators |
10.1002/anie.201611758 | 85,574,948 | Abstract The first crystallographically characterizable complex of Sc 2+ , [Sc(NR 2 ) 3 ] − (R=SiMe 3 ), has been obtained by LnA 3 /M reactions (Ln=rare earth metal; A=anionic ligand; M=alkali metal) involving reduction of Sc(NR 2 ) 3 with K in the presence of 2.2.2‐cryptand (crypt) and 18‐crown‐6 (18‐c‐6) and with Cs... | 10.1038/s41570-018-0059-x | This study presents the first crystallographically characterized ScII compound with amide ligands that reversibly binds N2 in an end-on fashion. This example highlights the fact that with the right ligand design, even group 3 low-valent early transition metal complexes can be stabilized. |
10.1002/anie.201505231 | 61,551,835 | Abstract Transition‐metal‐catalyzed radical reactions are becoming increasingly important in modern organic chemistry. They offer fascinating and unconventional ways for connecting molecular fragments that are often complementary to traditional methods. In particular, reductive radical additions to α,β‐unsaturated comp... | 10.1038/s41570-018-0059-x | This review highlights strategies for accessing catalytic single-electron chemistry with early transition metal complexes and their subsequent applications in Michael-type chemistry |
10.1126/science.aaf8505 | 83,042,382 | Characterizing the Zika virus antibody response Given the public health emergency that Zika virus poses, scientists are seeking to understand the Zika-specific immune response. Stettler et al. analyzed 119 monoclonal antibodies isolated from four donors that were infected with Zika virus during the present epidemic, in... | 10.1038/s41590-018-0210-3 | This paper provides in vivo evidence of serological interaction between DENV and ZIKV, demonstrating that antibodies to ZIKV can enhance DENV infection in mice |
10.1126/scitranslmed.aaa3787 | 62,250,647 | Dengue virus NS1 triggers endothelial permeability and vascular leak, and vaccination with NS1 induces a protective antibody response. | 10.1038/s41590-018-0210-3 | This paper, together with refs. 79,80 , shows that DENV NS1 is involved in the development of vascular leakage in mice |
10.1126/science.aaq0681 | 62,324,068 | Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of blastema formation had previously been hampered by the inability to identify and isolate blastema precursor cells in the adu... | 10.1038/s41576-020-0239-7 | This study uses single-cell transcriptome sequencing of connective tissue in regenerating axolotl limbs to detect a regeneration gene signature that precedes the emergence of an embryonic-like gene expression programme |
10.1126/science.aav9996 | 62,541,201 | Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential. To characterize this regenerative response, we performed single-cell RNA sequencing after tail amputation. By comparing naturally occurring regeneration-competent and -incompetent tadpoles, we identified a previously unrecognized cell type, whi... | 10.1038/s41576-020-0239-7 | By using a time series between regenerative and non-regenerative stages in Xenopus , the authors uncover a regeneration-specific gene expression signature |
10.1101/gr.233098.117 | 96,469,590 | One of the most important questions in regenerative biology is to unveil how and when genes change expression and trigger regeneration programs. The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specif... | 10.1038/s41576-020-0239-7 | This work profiles the enhancers from Drosophila imaginal discs that are active during regeneration and compares them to those in embryonic development and from other regeneration models |
10.1126/science.aau6173 | 20,125,505 | Whole-body regeneration is accompanied by complex transcriptomic changes, yet the chromatin regulatory landscapes that mediate this dynamic response remain unexplored. To decipher the regulatory logic that orchestrates regeneration, we sequenced the genome of the acoel worm Hofstenia miamia , a highly regenerative memb... | 10.1038/s41576-020-0239-7 | This article describes egr1 as a pioneer transcription factor and possible master regulator required for whole-body regeneration in the acoel worm Hofstenia miamia |
10.7554/elife.11588 | 82,807,449 | Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingless... | 10.1038/s41576-020-0239-7 | This study describes Polycomb-mediated decommissioning of an embryonic enhancer that limits regenerative capacity in Drosophila imaginal discs |
10.1242/dev.178632 | 83,310,450 | ABSTRACT Deciphering the genetic and epigenetic regulation of cardiomyocyte proliferation in organisms that are capable of robust cardiac renewal, such as zebrafish, represents an attractive inroad towards regenerating the human heart. Using integrated high-throughput transcriptional and chromatin analyses, we have ide... | 10.1038/s41576-020-0239-7 | This work shows that Polycomb activity can be pro-regenerative by promoting dedifferentiation through silencing sarcomeric genes in muscle |
10.1073/pnas.0506758102 | 20,885,623 | The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide... | 10.1038/s41576-020-0210-7 | The first work on pan-genomes in bacteria, this paper coined the term ‘pan-genome’ and the associated concepts of the ‘core’ and ‘dispensable’ genomes |
10.1182/blood.2020007488 | 107,187,708 | Abstract Venous thromboembolism (VTE) associated with cancer (CAT) is a well-described complication of cancer and a leading cause of death in patients with cancer. The purpose of this study was to assess potential associations of molecular signatures with CAT, including tumor-specific mutations and the presence of clon... | 10.1038/s41572-022-00336-y | In this analysis of patients with solid tumors, the authors identified multiple somatic mutations associated with the risk of thromboembolism |
10.1182/blood-2007-10-116327 | 104,247,221 | Abstract Risk of venous thromboembolism (VTE) is elevated in cancer, but individual risk factors cannot identify a sufficiently high-risk group of outpatients for thromboprophylaxis. We developed a simple model for predicting chemotherapy-associated VTE using baseline clinical and laboratory variables. The association ... | 10.1038/s41572-022-00336-y | This study investigated the first developed and validated risk tool for cancer-associated VTE; this tool has since been validated in multiple external cohorts and tested as an inclusion criterion in trials of outpatient thromboprophylaxis |
10.1182/blood-2017-03-743211 | 62,332,877 | Abstract Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we summarize common and cancer type–specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets, and tissue factor–positive (TF+) microvesicles (MVs) are all potential factors that alone or in com... | 10.1038/s41572-022-00336-y | This is a comprehensive overview of the basic and translational science underlying pathogenesis of cancer-associated thrombosis |
10.1002/ajh.25603 | 62,311,348 | Abstract Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high‐risk of VTE by the presence of risk factors. The National... | 10.1038/s41572-022-00336-y | Myeloma is a unique disease associated with a high risk of VTE in specific settings; this study develops and validates a risk tool for prediction of VTE in this specific setting |
10.1182/bloodadvances.2020001804 | 121,693,356 | Abstract Hospitalized patients with cancer are at an increased risk of developing venous thromboembolism (VTE). The recommendation for routine pharmacologic thromboprophylaxis in hospitalized patients with cancer to prevent VTE is based on extrapolation of results from noncancer cohorts. There are limited data to suppo... | 10.1038/s41572-022-00336-y | Inpatient thromboprophylaxis is recommended for hospitalized medically ill patients with cancer, but based on extrapolation from study populations largely without cancer; this pilot randomized study attempts to identify appropriate dosing of prophylaxis specifically for patients with cancer |
10.1111/j.1460-9568.2007.05440.x | 45,430,100 | Abstract Transcranial magnetic stimulation (TMS) is now widely used as a ‘virtual’ lesion paradigm to investigate behavioural functions, but the mechanisms through which it influences neural processing are unclear. To understand the differential effects of TMS on spatially overlapping populations of neurons we manipula... | 10.1038/s41583-022-00598-1 | This seminal article shows that neural adaptation modulates the behavioural and perceptual effects of TMS. The study inspired subsequent work on state-dependent TMS effects |
10.1093/cercor/bhaa007 | 42,526,721 | Abstract The ventral tegmental area (VTA) is a midbrain structure at the heart of the dopaminergic system underlying adaptive behavior. Endogenous firing rates of dopamine cells in the VTA vary from fast phasic bursts to slow tonic activity. Artificial perturbations of the VTA, through electrical or optogenetic stimula... | 10.1038/s41583-022-00598-1 | This study was among the first to systematically explore the global haemodynamic effects of electrical stimulation over a range of stimulation frequencies in anaesthetized and awake macaques |
10.1126/science.1117256 | 38,402,523 | When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premo... | 10.1038/s41583-022-00598-1 | This pioneering study uses combined TMS and EEG in humans to demonstrate dramatic alterations in cortical effective connectivity during sleep |
10.1126/science.aah7011 | 123,192,426 | A pulse of random activity is sufficient for a brain network to retrieve a dormant activity state. | 10.1038/s41583-022-00598-1 | This study applies multivariate decoding of EEG data to show that a TMS pulse can briefly reactivate the otherwise latent representation of an item held in working memory |
10.1073/pnas.1106439108 | 102,577,204 | Dorsolateral prefrontal cortex (DLPFC) is recruited during visual working memory (WM) when relevant information must be maintained in the presence of distracting information. The mechanism by which DLPFC might ensure successful maintenance of the contents of WM is, however, unclear; it might enhance neural maintenance ... | 10.1038/s41583-022-00598-1 | This combined TMS and fMRI study finds that stimulation over the DLPFC increases blood oxygen level-dependent activity in category-specific cortex during a working memory task, but only when visual distractors are present |
10.1038/s42003-020-0764-0 | 59,908,209 | Abstract Despite growing interest, the causal mechanisms underlying human neural network dynamics remain elusive. Transcranial Magnetic Stimulation (TMS) allows to noninvasively probe neural excitability, while concurrent fMRI can log the induced activity propagation through connected network nodes. However, this appro... | 10.1038/s41583-022-00598-1 | This study combines TMS, EEG and fMRI to show that neural oscillatory activity before stimulation constrains the propagation of TMS pulses within the cortico-subcortical motor network |
10.1038/s41467-018-04425-z | 38,337,787 | Abstract Mounting evidence suggests that inhibition of protein phosphatase-2A (PP2A), a serine/threonine phosphatase, could enhance anticancer immunity. However, drugs targeting PP2A are not currently available. Here, we report that a PP2A inhibitor, LB-100, when combined with anti-PD-1 (aPD-1) blockade can synergistic... | 10.1038/s41573-022-00618-w | This publication describes antitumour efficacy of PP2A/PP5 inhibitor LB-100 in combination with anti-PD1 in mice through a T cell-mediated action |
10.2337/db18-1362 | 96,410,076 | Genome-wide association studies have identified PTPN2 as an important non-MHC gene for autoimmunity. Single nucleotide polymorphisms that reduce PTPN2 expression have been linked with the development of various autoimmune disorders, including type 1 diabetes. The tyrosine phosphatase PTPN2 attenuates T-cell receptor an... | 10.1038/s41573-022-00618-w | This report demonstrates that selective deletion of TC-PTP in T cells of NOD mice on the non-obese diabetic background leads to accelerated diabetes onset and increased symptoms of colitis and Sjögren’s syndrome |
10.1186/s13075-020-02250-8 | 17,683,886 | Abstract Background The Src homology region 2 domain-containing phosphatase-1 (SHP-1) is known to exert negative regulatory effects on immune cell signaling. Mice with mutations in the Shp1 gene develop inflammatory skin disease and autoimmunity, but no arthritis. We sought to explore the role of SHP-1 in arthritis usi... | 10.1038/s41573-022-00618-w | This publication demonstrates that treatment with SHP1 activator regorafenib reduces arthritis incidence and severity in the proteoglycan-induced arthritis model |
10.1073/pnas.1807484116 | 122,332,430 | Phosphatase PP2A expression levels are positively correlated to the clinical severity of systemic lupus erythematosus (SLE) and IL17A cytokine overproduction, indicating a potential role of PP2A in controlling T H 17 differentiation and inflammation. By generating a mouse strain with ablation of the catalytic subunit α... | 10.1038/s41573-022-00618-w | This publication demonstrates that catalytic inactivation of PP2A in T cells or global PP2A inhibition is protective against EAE and reduces T H 17 cell differentiation in vitro and in vivo |
10.1038/s41467-019-10127-x | 103,471,000 | Abstract Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3 + cancer cells in v... | 10.1038/s41573-022-00618-w | This publication describes expression of PRL3 on the surface of cancer cells and the anti-tumour efficacy of PRL3-zumab, which targets the cancer cell surface-expressed PRL3 |
10.4049/jimmunol.162.2.677 | 139,063,586 | Abstract A novel cytokine from a thymic stromal cell line (thymic stromal lymphopoietin (TSLP)) promotes the development of B220+/IgM+ immature B cells when added to fetal liver cultures, long term bone marrow cultures, or bone marrow cells plated in semisolid medium. Because the activities of TSLP overlap with those o... | 10.1038/s41577-022-00735-y | The original study showing the existence of TSLP as a stromal factor that acts on both B and T cells |
10.1084/jem.20050199 | 123,156,792 | Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis. We now demonstrate that TSLP is required to mount a normal CD4+ T cell–mediated inflammatory response. TSLP acts directly on naive, but not, memory CD4+ T cells, and promotes their proliferation in response to antigen. In addition,... | 10.1038/s41577-022-00735-y | This study demonstrates a role for TSLP in allergic inflammation |
10.4049/jimmunol.178.11.6720 | 122,471,133 | Abstract Thymic stromal lymphopoietin (TSLP) is a cytokine that promotes CD4+ T cell homeostasis and contributes to allergic and inflammatory responses. TSLP can act directly on mouse CD4+ T cells, but in humans, the available data have indicated that TSLP receptors are not expressed on CD4+ T cells and that TSLP inste... | 10.1038/s41577-022-00735-y | The first demonstration of a direct effect of TSLP on human T cells, with TSLPR expression increased on activated CD4 + T cells |
10.1126/sciimmunol.aaf8471 | 17,300,452 | Thymic stromal lymphopoietin increases MRSA killing in a neutrophil- and complement-dependent manner. | 10.1038/s41577-022-00735-y | This study demonstrates that TSLP can promote the killing of methicillin-resistant S. aureus |
10.1038/ncomms14937 | 39,039,929 | Abstract The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) is pivotal to the pathophysiology of widespread allergic diseases mediated by type 2 helper T cell (Th2) responses, including asthma and atopic dermatitis. The emergence of human TSLP as a clinical target against asthma calls for maximally harne... | 10.1038/s41577-022-00735-y | This study shows the structure and mechanism of antagonism of the IL-7Rα–TSLPR complex, and further revealed the mechanism for tezepelumab for neutralizing TSLP function |
10.1182/blood.2020006846 | 61,278,872 | CRLF2-rearranged (CRLF2r) acute lymphoblastic leukemia (ALL) comprises over half of Philadelphia chromosome-like (Ph-like) ALL, is associated with poor outcome in children and adults. Overexpression of CRLF2 results in activation of JAK-STAT and parallel signaling pathways in experimental models, but existing small mol... | 10.1038/s41577-022-00735-y | This study shows that targeting of JAKs is effective treatment for CRLF2 -rearranged ALL |
10.1126/science.abd2893 | 132,904,275 | Sweat out the fat with TSLP! Thymic stromal lymphopoietin (TSLP) is a cytokine that can promote immune responses that characterize allergic diseases. Choa et al . found that mice engineered to produce elevated TSLP displayed selective white adipose tissue loss that protected them from obesity, insulin resistance, and s... | 10.1038/s41577-022-00735-y | This study shows that TSLP induces the loss of white adipose tissue and protects against obesity by promoting sebum hypersecretion |
10.1146/annurev-phyto-073009-114314 | 107,329,857 | Structural and functional genomics investigations are making an important impact on the current understanding and application of microbial agents used for plant disease control. Here, we review the case of Trichoderma spp., the most widely applied biocontrol fungi, which have been extensively studied using a variety of... | 10.1038/s41579-022-00819-5 | Review of early Trichoderma expressomes that have led to a better understanding of their complex interactions with other living organisms and their potential importance in agriculture and industry. |
10.3390/jof7040318 | 45,190,662 | There is no doubt that Trichoderma is an inhabitant of the rhizosphere that plays an important role in how plants interact with the environment. Beyond the production of cell wall degrading enzymes and metabolites, Trichoderma spp. can protect plants by inducing faster and stronger immune responses, a mechanism known a... | 10.1038/s41579-022-00819-5 | Description of Trichoderma -induced priming stages in plants and summary of the main regulatory nodes in the transcriptional network of systemic defence and growth promotion triggered by Trichoderma |
10.1007/s13225-020-00464-4 | 83,012,813 | Abstract Modern taxonomy has developed towards the establishment of global authoritative lists of species that assume the standardized principles of species recognition, at least in a given taxonomic group. However, in fungi, species delimitation is frequently subjective because it depends on the choice of a species co... | 10.1038/s41579-022-00819-5 | Unified criteria for molecular identification and systematics of Trichoderma species. |
10.1104/pp.108.130369 | 62,237,222 | Abstract Trichoderma species belong to a class of free-living fungi beneficial to plants that are common in the rhizosphere. We investigated the role of auxin in regulating the growth and development of Arabidopsis (Arabidopsis thaliana) seedlings in response to inoculation with Trichoderma virens and Trichoderma atrov... | 10.1038/s41579-022-00819-5 | Demonstration of the important role of auxin signalling in plant growth promotion by Trichoderma |
10.1111/mpp.12141 | 60,906,675 | Summary T richoderma is a soil‐borne fungal genus that includes species with a significant impact on agriculture and industrial processes. Some T richoderma strains exert beneficial effects in plants through root colonization, although little is known about how this interaction takes place. To better understand this pr... | 10.1038/s41579-022-00819-5 | Salicylic acid is key to controlling Trichoderma early root colonization as without the support of this phytohormone the plants cannot prevent the fungus from entering the vascular system and spreading to the aerial parts. |
10.1038/srep40216 | 62,149,489 | Abstract Root-knot nematodes (RKN) are major crop pathogens worldwide. Trichoderma genus fungi are recognized biocontrol agents and a direct activity of Trichoderma atroviride (Ta) against the RKN Meloidogyne javanica (Mj), in terms of 42% reduction of number of galls (NG), 60% of number of egg masses and 90% of number... | 10.1038/s41579-022-00819-5 | Plant responses to Trichoderma are heritable in terms of both induction of defence and growth promotion, and the expression of these traits in the offspring depends on the treatment to which the parental plant was subjected. |
10.1038/s41467-018-04926-x | 45,531,759 | Abstract Tolerance to antifungal drug concentrations above the minimal inhibitory concentration (MIC) is rarely quantified, and current clinical recommendations suggest it should be ignored. Here, we quantify antifungal tolerance in Candida albicans isolates as the fraction of growth above the MIC, and find that it is ... | 10.1038/s41579-019-0322-2 | This article provides a quantitative characterization of fluconazole tolerance in C. albicans distinguishing it from resistance and highlighting its phenotypic heterogeneity and association with subpopulation growth, and sensitivity to adjuvant drugs |
10.1128/jcm.02416-16 | 83,084,559 | ABSTRACT Breakpoints are used to predict whether an antifungal agent will be clinically effective against a particular fungal isolate. They are based on a combination of MIC values, pharmacokinetic/pharmacodynamic values, and clinical outcome data. For many fungus-antifungal combinations, these data might never be avai... | 10.1038/s41579-019-0322-2 | This review provides an important and accessible over-review of the concept of epidemiological cut-off values as well as the methodology that underlies their establishment |
10.1111/j.1365-2958.2012.08210.x | 82,468,635 | Summary The pathogenic yeast C andida albicans can develop resistance to the widely used antifungal agent fluconazole, which inhibits ergosterol biosynthesis. Resistance is often caused by gain‐of‐function mutations in the transcription factors Mrr 1, Tac 1 and Upc 2, which result in constitutive overexpression of mult... | 10.1038/s41579-019-0322-2 | This article shows that when a strain accumulates multiple resistance mutations that affect different transcription factors, the effects are independent and additive. In addition, these effects, generated by engineered deletion mutations, are associated with reduced fitness in the absence of drug stress. As many resist... |
10.1128/ec.00215-12 | 83,037,638 | ABSTRACT In Candida albicans , Upc2 is a zinc-cluster transcription factor that targets genes, including those of the ergosterol biosynthesis pathway. To date, three documented UPC2 gain-of-function (GOF) mutations have been recovered from fluconazole-resistant clinical isolates that contribute to an increase in ERG11 ... | 10.1038/s41579-019-0322-2 | This study establishes that gain-of-function mutations in , the key regulator of ergosterol biosynthesis gene expression, are a source of clinically important fluconazole resistance. Previously, only transcriptional regulators of efflux pump expression were known to do so. |
10.1128/aac.41.7.1482 | 79,784,959 | Resistance to antifungal drugs, specifically azoles such as fluconazole, in the opportunistic yeast Candida albicans has become an increasing problem in human immunodeficiency virus (HIV)-infected individuals. The molecular mechanisms responsible for this resistance have only recently become apparent and can include al... | 10.1038/s41579-019-0322-2 | This article presents the first detailed study of the molecular mechanisms underlying the development of fluconazole resistance over time in patients. It is a landmark study because of its patient-based approach and because it yielded strains that are still under study today |
10.1038/s41467-018-06944-1 | 41,497,072 | Abstract Fungal infections by drug-resistant Candida albicans pose a global public health threat. However, the pathogen’s diploid genome greatly hinders genome-wide investigations of resistance mechanisms. Here, we develop an efficient piggyBac transposon-mediated mutagenesis system using stable haploid C. albicans to ... | 10.1038/s41579-019-0322-2 | This study uses a haploid C. albicans isolate and a transposon mutagenesis system to identify mutants that are able to improve growth in very high fluconazole levels. However, the degree to which the mutants are resistant versus tolerant is not addressed, as drug responses did not include MIC assays. The study provides... |
10.1128/aac.01486-12 | 62,562,724 | ABSTRACT The echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. Echinocandins have good efficacy against Candida albicans but reduced activity against other Candida species, in particular Candida parapsilosis and Candida guilliermondii . Treatment of Candida albi... | 10.1038/s41579-019-0322-2 | This study finds that the ability of Candida species to grow in the presence of sub-MIC levels of caspofungin is associated with increased chitin levels in the cell wall. Pretreatment of cells with CaCl 2 and calcofluor white induces a similar increase in chitin and ability to grow in sub-MIC caspofungin levels. Whethe... |
10.1128/aac.00946-13 | 61,634,956 | ABSTRACT In the last decade, echinocandins have emerged as an important family of antifungal drugs because of their fungicidal activity against Candida spp. Echinocandins inhibit the enzyme β-1,3- d -glucan synthase, encoded by the FKS genes, and resistance to echinocandins is associated with mutations in this gene. In... | 10.1038/s41579-019-0322-2 | This study presents a detailed assessment of the cellular changes that accompany growth beyond the MIC in caspofungin as well as the effects that those changes have on fitness in mammalian hosts |
10.1002/art.10688 | 82,005,139 | Abstract Objective Neonatal‐onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investiga... | 10.1038/s41577-019-0165-0 | References 1–3 report that NLRP3 gain-of-function mutations promote human autoinflammatory diseases |
10.1073/pnas.0611496104 | 41,316,552 | The CATERPILLER (CLR/NLR) gene family encodes a family of putative nucleotide-binding proteins important for host defense. Although nucleotide binding is thought to be central to this family, this aspect is largely unstudied. The CATERPILLER protein cryopyrin/NALP3 regulates IL-1β processing by assembling the multimeri... | 10.1038/s41577-019-0165-0 | This study shows that ATP binding is essential for NLRP3 function, suggesting a therapeutic target for treating NLRP3-related diseases |
10.1126/science.aar7607 | 104,292,192 | Pyroptosis is a lytic form of cell death that is induced by inflammatory caspases upon activation of the canonical or noncanonical inflammasome pathways. These caspases cleave gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment, which executes pyroptosis by forming membrane pores. We found that calcium influx ... | 10.1038/s41580-020-0270-8 | Ruhl et al. demonstrate that the ESCRT machinery can protect cells from gasdermin-driven lysis at the early stages of pyroptosis |
10.1038/s41467-019-09753-2 | 125,150,255 | Abstract Caspase-1 activated in inflammasomes triggers a programmed necrosis called pyroptosis, which is mediated by gasdermin D (GSDMD). However, GSDMD-deficient cells are still susceptible to caspase-1-mediated cell death. Therefore, here, we investigate the mechanism of caspase-1-initiated cell death in GSDMD-defici... | 10.1038/s41580-020-0270-8 | This report demonstrates that caspase 1 can induce cell killing in the absence of gasdermin D |
10.1126/science.286.5445.1735 | 107,243,398 | Apoptosis can be triggered by members of the Bcl-2 protein family, such as Bim, that share only the BH3 domain with this family. Gene targeting in mice revealed important physiological roles for Bim. Lymphoid and myeloid cells accumulated, T cell development was perturbed, and most older mice accumulated plasma cells a... | 10.1038/s41580-020-0270-8 | Bouillet et al. provide the first demonstration that BH3-only proteins are essential for the initiation of apoptosis |
10.1002/ajmg.a.38245 | 80,998,708 | Lissencephaly (“smooth brain,” LIS) is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. The LIS spectrum includes agyria, pachygyria, and subcortical band heterotopia. Our first classification of LIS and subcortical band heterot... | 10.1038/s41582-020-0395-6 | A classification of the lissencephaly spectrum malformations: agyria, pachygyria and subcortical band heterotopia |
10.1111/epi.13319 | 80,930,184 | Summary Epilepsy surgery is an effective treatment in many patients with drug‐resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging ( MRI )—visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic ... | 10.1038/s41582-020-0395-6 | A standardized protocol for neuropathological work-up of epilepsy surgery specimens |
10.1126/science.abf5546 | 130,839,526 | Evolutionary development of the human brain is characterized by the expansion of various brain regions. Here, we show that developmental processes specific to humans are responsible for malformations of cortical development (MCDs), which result in developmental delay and epilepsy in children. We generated a human cereb... | 10.1038/s41582-022-00723-9 | Generation of a brain organoid model of tuberous sclerosis in this study changed the prevailing view of the disease by identifying a specific cell population in the caudal GE as the source of disease pathology |
10.1073/pnas.1315710110 | 20,421,745 | Significance Using 3D culture of human ES cells, we show new self-organizing aspects of human corticogenesis: spontaneous development of intracortical polarity, curving morphology, and complex zone separations. Moreover, this culture generates species-specific progenitors, outer radial glia, which are abundantly presen... | 10.1038/s41582-022-00723-9 | This study demonstrates self-organization of cortical tissue by generating neuronal tissue in vitro from human embryonic stem cells |
10.1126/science.aaf6116 | 104,271,249 | Zika virus tested in human brain organoids The pernicious and resilient Aedes mosquito is rapidly spreading Zika virus (ZIKV) through the Americas. ZIKV infection mostly causes mild disease, but in some patients, nervous system involvement is indicated. A particular worry is an observed correlation between infection of... | 10.1038/s41582-022-00723-9 | This study shows that Zika virus can infect human cortical progenitors in cerebral organoids and cause microcephaly-like phenotypes |
10.1126/science.abb5390 | 40,960,929 | Loss-of-function (LOF) screens provide a powerful approach to identify regulators in biological processes. Pioneered in laboratory animals, LOF screens of human genes are currently restricted to two-dimensional cell cultures, which hinders the testing of gene functions requiring tissue context. Here, we present CRISPR–... | 10.1038/s41582-022-00723-9 | In this study, massive parallel lineage tracing in organoids allowed high-throughput screening to simultaneously evaluate 172 microcephaly risk genes and uncovered endoplasmic reticulum secretion as a pathway involved in microcephaly |
10.1126/science.aav5386 | 62,112,572 | Disruptions in the ubiquitin protein ligase E3A ( UBE3A ) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remain... | 10.1038/s41582-022-00723-9 | In this study, cerebral organoids were used to model Angelman syndrome and uncovered dysregulation of large potassium channels as the underlying mechanism of hyperactivity phenotypes |
10.1126/science.aaz5626 | 62,328,391 | Cerebrospinal fluid (CSF) is a vital liquid, providing nutrients and signaling molecules and clearing out toxic by-products from the brain. The CSF is produced by the choroid plexus (ChP), a protective epithelial barrier that also prevents free entry of toxic molecules or drugs from the blood. Here, we establish human ... | 10.1038/s41582-022-00723-9 | In this study, a platform was developed for generating choroid plexus organoids that recapitulate the selective permeability of the human choroid plexus |
10.1126/science.1062538 | 81,044,023 | Clinical studies with the Abl tyrosine kinase inhibitor STI-571 in chronic myeloid leukemia demonstrate that many patients with advanced stage disease respond initially but then relapse. Through biochemical and molecular analysis of clinical material, we find that drug resistance is associated with the reactivation of ... | 10.1038/s41573-022-00615-z | This manuscript describes the first on-target resistance mutation to a targeted therapy |
10.1126/scitranslmed.3002003 | 41,758,322 | Lung cancers undergo dynamic genetic and histological changes upon developing resistance to EGFR inhibitors. | 10.1038/s41573-022-00615-z | This work demonstrates that lineage transformation from NSCLC to SCLC can be the cause of drug resistance in lung cancer |
10.1126/science.aav4474 | 83,430,669 | The emergence of drug resistance limits the efficacy of targeted therapies in human tumors. The prevalent view is that resistance is a fait accompli: when treatment is initiated, cancers already contain drug-resistant mutant cells. Bacteria exposed to antibiotics transiently increase their mutation rates (adaptive muta... | 10.1038/s41573-022-00615-z | This study shows that cancer cells can increase mutation rates under the stress of targeted therapy to generate resistant variants |
10.1038/ncomms5812 | 125,207,764 | Abstract Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families.... | 10.1038/s41579-019-0214-5 | This study reports the now standard sublineage typing scheme using SNP-based information for MTBC |
10.1183/13993003.01354-2017 | 83,364,687 | A clear understanding of the genetic basis of antibiotic resistance in Mycobacterium tuberculosis is required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence. Raw genotype–phenotype correlation data were extracted as part of a comprehensive systematic review to devel... | 10.1038/s41579-019-0214-5 | This was the first study to use a score system to classify mutations for clinical interpretation |
10.7717/peerj.4218 | 121,739,873 | Background Microbial genome sequencing is now being routinely used in many clinical and public health laboratories. Understanding how to report complex genomic test results to stakeholders who may have varying familiarity with genomics—including clinicians, laboratorians, epidemiologists, and researchers—is critical to... | 10.1038/s41579-019-0214-5 | This article reports new standards for reporting of WGS-based TB clinical information |
10.4049/jimmunol.1701755 | 20,428,322 | Abstract Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome–immune cross-talk contributes to neurodevelop... | 10.1038/s41577-019-0247-z | Together with reference 88 , this study illustrates the critical function of gut bacteria in pregnant dams in promoting neurodevelopmental disorder-like phenotypes in their offspring. |
10.1126/science.aac8260 | 125,154,352 | Peering into cathode layered oxides The quest for better rechargeable batteries means finding ways to pack more energy into a smaller mass or volume. Lithium layered oxides are a promising class of materials that could double storage capacities. However, the design of safe and long-lasting batteries requires an underst... | 10.1038/s41467-020-18736-7 | This work demonstrated a cooperative distortion of the oxygen framework associated with the anionic redox |
10.1515/psr-2018-0044 | 95,640,532 | Abstract Crystallography is a powerful descriptor of the atomic structure of solid-state matter and can be applied to analyse the phenomena present in functional materials. Especially for ion diffusion – one of the main processes found in electrochemical energy storage materials – crystallography can describe and evalu... | 10.1038/s41467-020-18736-7 | This review demonstrates the geometric and crystal-chemical approaches and methodologies to identify perspective electrochemical energy storage materials |
10.1126/science.1203486 | 62,608,967 | Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in canc... | 10.1038/s41568-020-00322-0 | This review summarizes an essential concept in the cancer immunology field regarding the interaction between the immune system and cancer cells during cancer development, ‘cancer immuno-editing’ |
10.1126/science.aaa1348 | 20,841,536 | Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death... | 10.1038/s41568-020-00322-0 | Together with McGranahan et al. (2016), this paper shows the importance of the TMB in the efficacy of ICIs |
10.1126/sciimmunol.aav3937 | 19,835,284 | The clinical efficacy of anti–PD-1 (programmed cell death–1) monoclonal antibody (mAb) against cancers with oncogenic driver gene mutations, which often harbor a low tumor mutation burden, is variable, suggesting different contributions of each driver mutation to immune responses. Here, we investigated the immunologica... | 10.1038/s41568-020-00322-0 | This study shows an immunological role of EGFR signalling: aberrant EGFR signalling recruits T reg cells in the TME via chemokine production |
10.1111/cas.13860 | 83,179,865 | The efficacy of programmed cell death–1 ( PD ‐1) blockade in patients with non–small cell lung cancer ( NSCLC ) positive for epidermal growth factor receptor ( EGFR ) gene mutations has been found to be limited, but the underlying mechanisms for this poor response have remained obscure. Given that the recognition by T ... | 10.1038/s41568-020-00322-0 | This study shows that aberrant EGFR signalling inhibits MHC class I expression |
10.1126/science.1063916 | 20,881,220 | The localization of γδ T cells within epithelia suggests that these cells may contribute to the down-regulation of epithelial malignancies. We report that mice lacking γδ cells are highly susceptible to multiple regimens of cutaneous carcinogenesis. After exposure to carcinogens, skin cells expressed Rae-1 and H60, maj... | 10.1038/s41568-019-0153-5 | Seminal work using TCR δ chain −/− mice to demonstrate a protective role for mouse γδ T cells in chemically induced skin cancer |
10.1038/ncomms12080 | 6,408,309 | Abstract The skin is under constant renewal and exposure to environmental challenges. How homeostasis is maintained alongside protective mechanisms against damage is unclear. Among the basal epithelial cells (ECs) is a population of resident intraepithelial lymphocytes (IELs) that provide host-protective immune surveil... | 10.1038/s41568-019-0153-5 | A study showing a crucial effect of IL-13-producing γδ T cells in maintaining skin integrity and therefore protecting from carcinogenesis |
10.1073/pnas.1403424111 | 41,681,522 | Significance Tumor development is impacted by a set of diverse infiltrating leukocyte populations that can either inhibit or, paradoxically, enhance tumor cell growth. This study characterizes a cellular cross-talk between γδ T lymphocytes and small peritoneal macrophages (SPMs) that is mediated by the proinflammatory ... | 10.1038/s41568-019-0153-5 | The description of a pro-tumour axis between mouse IL-17-producing γδ T cells and pro-inflammatory and pro-angiogenic macrophages in an ovarian cancer mouse model |
10.1182/blood-2002-12-3665 | 81,543,969 | Abstract There is increasing evidence that γδ T cells have potent innate antitumor activity. We described previously that synthetic aminobisphosphonates are potent γδ T cell stimulatory compounds that induce cytokine secretion (ie, interferon γ [IFN-γ]) and cell-mediated cytotoxicity against lymphoma and myeloma cell l... | 10.1038/s41568-019-0153-5 | A pioneering clinical trial showing the safety and efficacy of in vivo Vγ9Vδ2 T cell activation in patients with lymphoma |
10.1182/blood-2010-12-325993 | 83,044,662 | Abstract Major limitations of currently investigated αβT cells redirected against cancer by transfer of tumor-specific αβTCR arise from their low affinity, MHC restriction, and risk to mediate self-reactivity after pairing with endogenous α or βTCR chains. Therefore, the ability of a defined γ9δ2TCR to redirect αβT cel... | 10.1038/s41568-019-0153-5 | A work that establishes a proof of principle for transferring Vγ9Vδ2 TCRs into αβ T cells to improve their antitumour efficacy and safety |
10.1182/blood-2012-05-430470 | 41,678,973 | Abstract Human peripheral Vγ9Vδ2 T cells are activated by phosphorylated metabolites (phosphoagonists [PAg]) of the mammalian mevalonate or the microbial desoxyxylulose-phosphate pathways accumulated by infected or metabolically distressed cells. The underlying mechanisms are unknown. We show that treatment of nonsusce... | 10.1038/s41568-019-0153-5 | A seminal paper on butyrophilin subfamily 3 member A1 and its role in inducing cellular stress-sensing by human Vγ9Vδ2 T cells |
10.1534/genetics.107.074963 | 61,157,339 | Abstract The synthesis of biotin, a vitamin required for many carboxylation reactions, is a variable trait in Saccharomyces cerevisiae. Many S. cerevisiae strains, including common laboratory strains, contain only a partial biotin synthesis pathway. We here report the identification of the first step necessary for the ... | 10.1038/s41579-018-0075-3 | This study shows that the biotin pathway in the baker’s yeast, whose five of the six genes reside in two subtelomeric gene clusters, was lost in an ancestor but was subsequently rebuilt through acquisition of bacterial genes via HGT and gene duplication followed by neofunctionalization |
10.1073/pnas.1304461110 | 81,549,282 | Genomic analyses have proliferated without being tied to tangible phenotypes. For example, although coordination of both gene expression and genetic linkage have been offered as genetic mechanisms for the frequently observed clustering of genes participating in fungal metabolic pathways, elucidation of the phenotype(s)... | 10.1038/s41579-018-0075-3 | This study shows that fungal metabolic genes that handle toxic compounds are more likely to be clustered, suggesting that the phenotype selection acts on to drive gene clustering is the mitigation of toxicity of pathway intermediates |
10.1073/pnas.1313258110 | 20,631,068 | Significance Filamentous fungi are well known for their ability to produce a wide range of natural products. Until now, biosynthetic genes contiguously aligned in a cluster have been associated with the production of a distinct natural product. This work demonstrates an additional layer of complexity in fungal secondar... | 10.1038/s41579-018-0075-3 | This study is the first to report the existence of intertwined MGCs responsible for the production of at least two distinct secondary metabolites in fungal genomes |
10.1073/pnas.142307199 | 59,722,839 | Filamentous fungi within the Fusarium graminearum species complex ( Fg complex) are the primary etiological agents of Fusarium head blight (scab) of wheat and barley. Scab is an economically devastating plant disease that greatly limits grain yield and quality. In addition, scabby grain is often contaminated with trich... | 10.1038/s41579-018-0075-3 | This is the first study to report evidence for trans-specific polymorphism in the gene cluster of the trichothecene mycotoxin, which is maintained by balancing selection acting on chemotype differences |
10.1111/j.1365-294x.2009.04414.x | 82,588,431 | Abstract Aflatoxins produced by Aspergillus flavus are potent carcinogens that contaminate agricultural crops. Recent efforts to reduce aflatoxin concentrations in crops have focused on biological control using nonaflatoxigenic A. flavus strains AF36 (=NRRL 18543) and NRRL 21882 (the active component of afla‐guard ® ).... | 10.1038/s41579-018-0075-3 | Extensive analysis of patterns of linkage disequilibrium in the aflatoxin gene cluster of A. flavus suggests that recombination events are unevenly distributed across the cluster, including the absence of recombination for the subcluster of genes acting early in the aflatoxin synthesis pathway. |
10.1093/brain/awab388 | 132,706,019 | Abstract Dural sinuses were recently identified as a hub for peripheral immune surveillance of brain-derived antigens cleared through CSF. However, animal studies have also indicated that substances and cells may enter the intracranial compartment directly from bone marrow. We used MRI and a CSF tracer to investigate i... | 10.1038/s41586-022-05474-7 | This study reveals how the CSF efflux routes to the skull bone marrow observed in rodents are conserved in humans. |
10.1126/science.abf7844 | 80,874,304 | The meninges are a membranous structure enveloping the central nervous system (CNS) that host a rich repertoire of immune cells mediating CNS immune surveillance. Here, we report that the meninges contain a pool of monocytes and neutrophils supplied not from the blood, but by adjacent skull and vertebral bone marrow. U... | 10.1038/s41586-022-05474-7 | This study highlights how the CNS-associated bone marrow can supply myeloid cells to the brain and spinal cord meninges under homeostasis and during diverse pathologies. |
10.1126/science.abf9277 | 103,022,509 | The meninges contain adaptive immune cells that provide immunosurveillance of the CNS. These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which... | 10.1038/s41586-022-05474-7 | This study demonstrates how the CNS-associated bone marrow can supply B cells to the meninges and how the meninges function as an active site for B cell maturation. |
10.1038/s41467-019-14195-x | 102,422,907 | Abstract The mechanisms behind molecular transport from cerebrospinal fluid to dural lymphatic vessels remain unknown. This study utilized magnetic resonance imaging along with cerebrospinal fluid tracer to visualize clearance pathways to human dural lymphatics in vivo. In 18 subjects with suspicion of various types of... | 10.1038/s41586-022-05474-7 | This study reveals how the CSF efflux routes to the dural sinuses observed in rodents are conserved in humans. |
10.1084/jem.20142290 | 20,798,614 | The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater ... | 10.1038/s41586-022-05474-7 | This study demonstrates the presence of a lymphatic network in the dural meninges that drains CSF. |
10.1084/jem.20220035 | 130,829,121 | Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extra... | 10.1038/s41586-022-05474-7 | This study highlights the key pathways for lymphatic drainage of CSF in rodents and demonstrates how these are conserved in humans. |
10.1073/pnas.0804931105 | 15,896,742 | Late-life loss of independence in daily living is a central concern for the aging individual and for society. The implications of increased survival to advanced age may be different at the population level than at the individual level. Here we used a longitudinal multi-assessment survey of the entire Danish 1905 cohort... | 10.1038/s41586-018-0457-8 | A survey of a Danish cohort born in 1905 and followed for physical and cognitive independence from 1998 to 2005 across the age range of 92–100 years shows that lifespan extension of a population does not necessarily results in exceptional levels of disability at high ages |
10.1073/pnas.0809594106 | 104,107,000 | The human forkhead box O3A gene ( FOXO3A ) encodes an evolutionarily conserved key regulator of the insulin–IGF1 signaling pathway that is known to influence metabolism and lifespan in model organisms. A recent study described 3 SNPs in the FOXO3A gene that were statistically significantly associated with longevity in ... | 10.1038/s41586-018-0457-8 | A genetic variant in FOXO3A , rs2802292, is associated with longevity in humans |
10.1126/scitranslmed.aai8700 | 123,018,746 | A periodic fasting diet improves markers of metabolic dysfunction, particularly in people already at risk. | 10.1038/s41586-018-0457-8 | Healthy human subjects randomly allocated to a diet that mimics fasting, which is low in calories, sugars and protein, but high in unsaturated fats, as opposed to unrestricted food consumption, showed reduced body weight, trunk and total body fat, had lower blood pressure and decreased levels of IGF-1, with more marked... |
10.1126/scitranslmed.3009892 | 20,628,113 | mTOR inhibition by RAD001 improves immune responses in elderly volunteers receiving an influenza vaccination. | 10.1038/s41586-018-0457-8 | At doses that were well-tolerated, the mTOR inhibitor RAD001 enhanced the response to the influenza vaccine in elderly volunteers by about 20% and reduced the percentage of CD4 + and CD8 + T lymphocytes that expressed the programmed death-1 receptor, which inhibits T cell signalling and shows higher expression with inc... |
10.1073/pnas.1105777108 | 82,951,195 | Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundanc... | 10.1038/s41565-022-01250-w | The first study to show the unexpected efficacy of cationic dendrimers in treating pathogen-associated molecular pattern-induced acute liver injury |
10.1126/sciadv.abj2372 | 133,014,297 | A therapeutic strategy that targets multiple proinflammatory factors in inflammatory bowel disease (IBD) with minimal systemic side effects would be attractive. Here, we develop a drug-free, biodegradable nanomedicine that acts against IBD by scavenging proinflammatory cell-free DNA (cfDNA) and reactive oxygen species ... | 10.1038/s41565-022-01250-w | A study demonstrating the use of cationic nanoparticles to treat an inflammatory disease. |
10.1158/1078-0432.ccr-13-0458 | 104,148,390 | Abstract Purpose: To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression. Experimental Design: We examined whether administration of a PD-1 bloc... | 10.1038/s41577-021-00539-6 | This is one of the first studies to show that anti-PD1 immunotherapy can increase CAR T cell efficacy in a solid cancer setting |
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