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3883485
Replacement of mitochondria through nuclear transfer between oocytes of two different women has emerged recently as a strategy for preventing inheritance of mtDNA diseases. Although experiments in human oocytes have shown effective replacement, the consequences of small amounts of mtDNA carryover have not been studied ...
Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes.
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3893473
TAL (transcription activator-like) effectors constitute a novel class of DNA-binding proteins with predictable specificity. They are employed by Gram-negative plant-pathogenic bacteria of the genus Xanthomonas which translocate a cocktail of different effector proteins via a type III secretion system (T3SS) into plant ...
TAL effectors are remote controls for gene activation.
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3896759
Blood and lymphatic vessels pervade almost all body tissues and have numerous essential roles in physiology and disease. The inner lining of these networks is formed by a single layer of endothelial cells, which is specialized according to the needs of the tissue that it supplies. Whereas the general mechanisms of bloo...
Vascular heterogeneity and specialization in development and disease
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3898784
Importance Although non–vitamin K antagonist oral anticoagulants (NOACs) are increasingly used to prevent thromboembolic disease, there are limited data on NOAC-related intracerebral hemorrhage (ICH). Objective To assess the association between preceding oral anticoagulant use (warfarin, NOACs, and no oral anticoagulan...
Association of Intracerebral Hemorrhage Among Patients Taking Non–Vitamin K Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital Mortality
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3899896
Several studies have reported that elevated red blood cell distribution width (RDW) was associated with the poor prognosis of different kinds of cancers. The aim of this study was to investigate the prognostic role of RDW in patients undergoing resection for nonmetastatic rectal cancer. We retrospectively reviewed a da...
Elevated red blood cell distribution width contributes to poor prognosis in patients undergoing resection for nonmetastatic rectal cancer
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3903084
Objective: To examine different health outcomes that are associated with specific lifestyle and genetic factors. Materials and methods: From March 2004 to April 2006, a sample of employees from three different health and academic institutions, as well as their family members, were enrolled in the study after providing ...
Health workers cohort study: methods and study design.
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3912660
OBJECTIVE Corin is a serine protease that converts pro-atrial natriuretic peptide (pro-ANP) to atrial natriuretic peptide (ANP), a cardiac hormone that regulates salt-water balance and blood pressure. ANP is degraded by natriuretic peptide receptor (NPR). This study was to determine if aberrant pro-ANP/corin/NPR signal...
Aberrant pro-atrial natriuretic peptide/corin/natriuretic peptide receptor signaling is present in maternal vascular endothelium in preeclampsia.
{"1011": 0.029824240133166313, "1998": 0.011650617234408855, "2001": 0.021256839856505394, "2005": 0.05046287178993225, "2007": 0.3248254358768463, "2020": 0.01934296265244484, "2050": 0.9045027494430542, "2062": 0.20660123229026794, "2063": 0.20739519596099854, "2064": 0.2160874605178833, "2078": 0.4734157919883728, "...
3929361
BACKGROUND Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) an...
Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance
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3930020
Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis....
Role of the Parasite-Derived Prostaglandin D2 in the Inhibition of Epidermal Langerhans Cell Migration during Schistosomiasis Infection
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3935126
Background In a phase 1 trial, axicabtagene ciloleucel (axi‐cel), an autologous anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy, showed efficacy in patients with refractory large B‐cell lymphoma after the failure of conventional therapy. Methods In this multicenter, phase 2 trial, we enrolled 111 patients with...
Axicabtagene Ciloleucel CAR T‐Cell Therapy in Refractory Large B‐Cell Lymphoma
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3943235
During physiological or psychological stress, catecholamines produced by the sympathetic nervous system (SNS) regulate the immune system. Previous studies report that the activation of β-adrenergic receptors (βARs) mediates the actions of catecholamines and increases pro-inflammatory cytokine production in a number of ...
Beta adrenergic blockade decreases the immunomodulatory effects of social disruption stress
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3944632
CONTEXT In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. OBJECTIVE To determine if WBRT combined with SRS results in improvements in surviva...
Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.
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3952288
Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4+3− inducer cell population, previously linked to ...
RANK signals from CD4+3− inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla
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3960385
Proteomics can be used to characterize quality defects including pale, soft, and exudative (PSE) meat (pork and poultry), woody broiler breast meat, reddish catfish fillets, meat toughness, and beef myoglobin oxidation. PSE broiler meat was characterized by 15 proteins that differed in abundance in comparison to normal...
Proteomic approach to characterize biochemistry of meat quality defects.
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3973445
Adenosine 5′-monophosphate–activated protein kinase (AMPK) is a pivotal regulator of metabolism at cellular and organismal levels. AMPK also suppresses inflammation. We found that pharmacological activation of AMPK rapidly inhibited the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway ...
Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling
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3981033
The cellular inhibitors of apoptosis (cIAP) 1 and 2 are amplified in about 3% of cancers and have been identified in multiple malignancies as being potential therapeutic targets as a result of their role in the evasion of apoptosis. Consequently, small-molecule IAP antagonists, such as LCL161, have entered clinical tri...
IAP antagonists induce anti-tumor immunity in multiple myeloma
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3981244
Sexual health severely decreases with age. For males older than 40 years, erectile dysfunction (ED) is the most common sexual disorder. Although physical and psychological risk factors for ED have been identified, protective factors are yet to be determined. To date, no study has examined endocrine and psychosocial fac...
Psychobiological Protective Factors Modifying the Association Between Age and Sexual Health in Men: Findings From the Men’s Health 40+ Study
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3981613
Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how th...
Patient-derived induced pluripotent stem cells in cancer research and precision oncology
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3981729
TAL (transcription activator-like) effectors, secreted by phytopathogenic bacteria, recognize host DNA sequences through a central domain of tandem repeats. Each repeat comprises 33 to 35 conserved amino acids and targets a specific base pair by using two hypervariable residues [known as repeat variable diresidues (RVD...
Structural basis for sequence-specific recognition of DNA by TAL effectors.
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3984231
Adverse remodeling following myocardial infarction (MI) leading to heart failure is driven by an imbalanced resolution of inflammation. The macrophage cell is an important control of post-MI inflammation, as macrophage subtypes secrete mediators to either promote inflammation and extend injury (M1 phenotype) or suppres...
Caveolin-1 deletion exacerbates cardiac interstitial fibrosis by promoting M2 macrophage activation in mice after myocardial infarction.
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3986403
Study of the role of hydroperoxides and lipid peroxidation in disease requires simple and sensitive methods for direct hydroperoxide measurement. We report on a technique for measuring hydroperoxide which relies upon the rapid hydroperoxide-mediated oxidation of Fe2+ under acidic conditions. Fe3+ forms a chromophore wi...
Lipid hydroperoxide measurement by oxidation of Fe2+ in the presence of xylenol orange. Comparison with the TBA assay and an iodometric method
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4020950
Exosomes are extracellular vesicles of endosomal origin which have emerged as key mediators of intercellular communication. All major cardiac cell types-including cardiomyocytes, endothelial cells, and fibroblasts-release exosomes that modulate cellular functions. Exosomes released from human cardiac progenitor cells (...
Roles of exosomes in cardioprotection.
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4036038
Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflectin...
The rate of change in declining steroid hormones: a new parameter of healthy aging in men?
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4037034
Epstein-Barr virus (EBV) episomes are stably maintained in permissive proliferating cell lines due to EBV nuclear antigen 1 (EBNA-1) protein-mediated replication and segregation. Previous studies showed the ability of EBV episomes to confer long-term transgene expression and correct genetic defects in deficient cells. ...
Development of a novel helper-dependent adenovirus-Epstein-Barr virus hybrid system for the stable transformation of mammalian cells.
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4067274
Differential splice site pairing establishes alternative splicing patterns resulting in the generation of multiple mRNA isoforms. This process is carried out by the spliceosome, which is activated by a series of sequential structural rearrangements of its five core snRNPs. To determine when splice sites become function...
Spliceosome assembly pathways for different types of alternative splicing converge during commitment to splice site pairing in the A complex.
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4085204
The male hypermethylated (MHM) region, located near the middle of the short arm of the Z chromosome of chickens, consists of approximately 210 tandem repeats of a BamHI 2.2-kb sequence unit. Cytosines of the CpG dinucleotides of this region are extensively methylated on the two Z chromosomes in the male but much less m...
Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus
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4138659
Macropinocytosis is a highly conserved endocytic process by which extracellular fluid and its contents are internalized into cells through large, heterogeneous vesicles known as macropinosomes. Oncogenic Ras proteins have been shown to stimulate macropinocytosis but the functional contribution of this uptake mechanism ...
Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
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4162857
RNA processing is carried out in close proximity to the site of transcription, suggesting a regulatory link between transcription and pre-mRNA splicing. Using an in vitro transcription/splicing assay, we demonstrate that an association of RNA polymerase II (Pol II) transcription and pre-mRNA splicing is required for ef...
Linking Splicing to Pol II Transcription Stabilizes Pre-mRNAs and Influences Splicing Patterns
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4164929
Skeletal muscle extracellular matrix remodelling has been proposed as a new feature associated with obesity and metabolic dysfunction. Exercise training improves muscle function in obesity, which may be mediated by regulatory effects on the muscle extracellular matrix. This review examined available literature on skele...
The emerging role of skeletal muscle extracellular matrix remodelling in obesity and exercise.
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4200695
OBJECTIVE To evaluate if a specific exercise strategy, targeting the rotator cuff and scapula stabilisers, improves shoulder function and pain more than unspecific exercises in patients with subacromial impingement syndrome, thereby decreasing the need for arthroscopic subacromial decompression. DESIGN Randomised, part...
Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study
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4231060
The transforming gene (src) of avian sarcoma virus (ASV) and adjacent regions of the viral genome have been isolated by molecular cloning of viral DNA. Their nucleotide sequence encompasses the whole of src and the portion of the gene env that encodes gp 37, one of two glycoproteins found in the viral envelope. Src enc...
Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product
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4246523
Recognizing that the current MDR-TB regimen is suboptimal and based on low-quality evidence, the Global MDR-TB Clinical Trials Landscape Meeting was held in December, 2014 to strategize about coordination of research and development of new treatment regimens for this disease that affects millions of people worldwide ev...
Issues in design and interpretation of MDR-TB clinical trials: report of the first Global MDR-TB Clinical Trials Landscape Meeting
{"1009": 0.17840765416622162, "1011": 0.1693800985813141, "1018": 0.06612417846918106, "1038": 0.3883931338787079, "1045": 0.7898768186569214, "1996": 0.436867892742157, "1999": 0.06246116757392883, "2011": 0.4879087805747986, "2013": 0.5232481360435486, "2022": 0.007782140281051397, "2029": 0.2637155055999756, "2033":...
4254064
DEFINITIVE erythropoiesis in birds originates from stem cells that emerge in the splanchnopleural mesoderm near the embryonic aorta1–4. The yolk sac is still generally held to be the unique provider of haematopoietic stem cells during mammalian ontogeny5, although there may be an alternative intraembryonic source of st...
Para-aortic splanchnopleura from early mouse embryos contains B1a cell progenitors
{"1052": 0.2089812457561493, "1996": 0.004870930220931768, "1999": 0.25694093108177185, "2004": 0.12986256182193756, "2011": 0.006812678650021553, "2013": 0.4574742913246155, "2024": 0.11517547070980072, "2029": 0.05046287178993225, "2031": 0.18492233753204346, "2038": 0.06886265426874161, "2042": 0.2741633653640747, "...
4256553
Pluripotential cells are present in a mouse embryo until at least an early post-implantation stage, as shown by their ability to take part hi the formation of chimaeric animals1 and to form teratocarcinomas2. Until now it has not been possible to establish progressively growing cultures of these cells in vitro, and cel...
Establishment in culture of pluripotential cells from mouse embryos
{"1009": 0.4920966327190399, "1011": 0.39893341064453125, "1015": 0.056018441915512085, "1016": 0.10906458646059036, "1018": 0.35403475165367126, "1022": 0.2026219218969345, "1043": 0.5092619061470032, "1045": 0.4196864068508148, "1049": 1.0775588750839233, "1056": 0.987156867980957, "1155": 0.2741633653640747, "1156":...
4270992
INTERACTIONS between major histocompatibility complex (MHC) molecules and the CD4 or CDS coreceptors have a major role in intrathymic T-cell selection1. On mature T cells, each of these two glycoproteins is associated with a class-specific bias in MHC molecule recognition by the T-cell receptor. CD4+ T cells respond to...
MHC class II interaction with CD4 mediated by a region analogous to the MHC class I binding site for CD8
{"1996": 0.09761575609445572, "1997": 0.28743788599967957, "2011": 0.20739519596099854, "2012": 0.2478361576795578, "2013": 0.09228714555501938, "2029": 0.06977381557226181, "2031": 0.015504186972975731, "2038": 0.21765978634357452, "2049": 0.0174254160374403, "2053": 0.17840765416622162, "2054": 0.3499138653278351, "2...
4283694
Although DNA is the carrier of genetic information, it has limited chemical stability. Hydrolysis, oxidation and nonenzymatic methylation of DNA occur at significant ratesin vivo, and are counteracted by specific DNA repair processes. The spontaneous decay of DNA is likely to be a major factor in mutagenesis, carcinoge...
Instability and decay of the primary structure of DNA
{"1011": 0.030771657824516296, "1043": 0.6931471824645996, "1997": 0.06795065850019455, "2000": 0.0770333781838417, "2012": 0.15023678541183472, "2015": 0.08692999184131622, "2028": 0.015504186972975731, "2037": 0.043007105588912964, "2054": 0.004870930220931768, "2064": 0.029824240133166313, "2079": 0.1468697786331176...
4300851
A major goal of biology is to provide a quantitative description of cellular behaviour. This task, however, has been hampered by the difficulty in measuring protein abundances and their variation. Here we present a strategy that pairs high-throughput flow cytometry and a library of GFP-tagged yeast strains to monitor r...
Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise
{"1011": 0.03266380727291107, "1017": 0.05694137513637543, "1018": 0.33115679025650024, "1998": 0.0038986403960734606, "2004": 0.4673144817352295, "2005": 0.053244512528181076, "2011": 0.018384648486971855, "2013": 0.32129061222076416, "2015": 0.04674193635582924, "2022": 0.025073638185858727, "2026": 0.617084145545959...
4303075
Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription...
Direct conversion of fibroblasts to functional neurons by defined factors
{"1050": 0.2231435477733612, "1056": 0.3027053773403168, "1155": 0.4444103240966797, "1999": 0.4574742913246155, "2002": 0.969535231590271, "2003": 0.3622259199619293, "2011": 0.055094651877880096, "2046": 0.08692999184131622, "2053": 0.06154331564903259, "2088": 0.04207121208310127, "2094": 0.960606575012207, "2182": ...
4303939
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension...
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
{"1011": 0.12470348179340363, "1055": 0.083342544734478, "1059": 0.2026219218969345, "1996": 0.20977331697940826, "1997": 0.006812678650021553, "2003": 0.7201237678527832, "2011": 0.31560876965522766, "2012": 0.10291612148284912, "2022": 0.29400965571403503, "2024": 0.040196798741817474, "2029": 0.28963330388069153, "2...
4305576
Chromatin allows the eukaryotic cell to package its DNA efficiently. To understand how chromatin structure is controlled across the Saccharomyces cerevisiae genome, we have investigated the role of the ATP-dependent chromatin remodelling complex Isw2 in positioning nucleosomes. We find that Isw2 functions adjacent to p...
Chromatin remodelling at promoters suppresses antisense transcription
{"1011": 0.32270604372024536, "1040": 0.0752234235405922, "1060": 0.18167030811309814, "1996": 0.12470348179340363, "1997": 0.06337817758321762, "1999": 0.06429435312747955, "2002": 0.10731173306703568, "2005": 0.11951763927936554, "2007": 0.2539152204990387, "2011": 0.1808556467294693, "2012": 0.16359257698059082, "20...
4306711
Human mitochondrial ribosomes are specialized in the synthesis of 13 proteins, which are fundamental components of the oxidative phosphorylation system. The pathway of mitoribosome biogenesis, the compartmentalization of the process, and factors involved remain largely unknown. Here, we have identified the DEAD-box pro...
The Human Mitochondrial DEAD-Box Protein DDX28 Resides in RNA Granules and Functions in Mitoribosome Assembly.
{"1011": 0.28890204429626465, "1038": 0.1930064558982849, "1043": 0.34922540187835693, "1052": 0.02792670577764511, "1156": 0.630689799785614, "2004": 0.14095009863376617, "2013": 0.1734936386346817, "2029": 0.11081436276435852, "2031": 0.1808556467294693, "2038": 0.07068414986133575, "2043": 0.11604541540145874, "2044...
4311206
Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (r...
Conversion of Adult Pancreatic α-cells to β-cells After Extreme β-cell Loss
{"1011": 0.07793712615966797, "1017": 0.21372433006763458, "1043": 0.9944084882736206, "1044": 0.25995752215385437, "1047": 0.38174858689308167, "1052": 0.08244366943836212, "1056": 0.42926809191703796, "1060": 0.09672962874174118, "1155": 0.3262358605861664, "2003": 0.2493593990802765, "2010": 0.7710843086242676, "201...
4312169
Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutatio...
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
{"1052": 0.5080875158309937, "1997": 0.058784693479537964, "2003": 0.06337817758321762, "2008": 0.02887592278420925, "2011": 0.3283478021621704, "2013": 0.015504186972975731, "2015": 0.26146242022514343, "2031": 0.02792670577764511, "2039": 0.018384648486971855, "2048": 0.13157635927200317, "2057": 0.003898640396073460...
4313478
Most eukaryotic genes are interrupted by non-coding introns that must be accurately removed from pre-messenger RNAs to produce translatable mRNAs. Splicing is guided locally by short conserved sequences, but genes typically contain many potential splice sites, and the mechanisms specifying the correct sites remain poor...
Translational control of intron splicing in eukaryotes
{"1011": 0.02792670577764511, "1017": 0.14179791510105133, "1018": 0.2800849378108978, "1044": 0.19862671196460724, "1156": 0.47036975622177124, "1996": 0.5903874635696411, "1999": 0.020300358533859253, "2029": 0.12728634476661682, "2035": 0.07431721687316895, "2037": 0.17840765416622162, "2043": 0.15526613593101501, "...
4319174
All homeotherms use thermogenesis to maintain their core body temperature, ensuring that cellular functions and physiological processes can continue in cold environments. In the prevailing model of thermogenesis, when the hypothalamus senses cold temperatures it triggers sympathetic discharge, resulting in the release ...
Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis
{"1011": 0.04487626627087593, "1020": 0.46486347913742065, "1054": 0.5483922958374023, "1997": 0.21214580535888672, "2003": 0.09584271162748337, "2004": 0.2501201331615448, "2008": 0.012615402229130268, "2011": 0.2667117714881897, "2012": 0.1751343309879303, "2029": 0.19782574474811554, "2050": 0.10467668622732162, "20...
4319844
Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that occurs in a subset of cancers. By analyzing telomerase-positive cells and their human TERC knockout-derived ALT human cell lines, we show that ALT cells harbor more fragile telomeres representing telomere replicat...
Alternative Lengthening of Telomeres Mediated by Mitotic DNA Synthesis Engages Break-Induced Replication Processes.
{"1037": 0.0009760859538801014, "1996": 0.022212404757738113, "1997": 0.11517547070980072, "1999": 0.004870930220931768, "2008": 0.030771657824516296, "2011": 0.4145384132862091, "2013": 0.055094651877880096, "2029": 0.18167030811309814, "2031": 0.08513788133859634, "2036": 0.0029254043474793434, "2037": 0.250880300998...
4320111
The expression of clock genes in vertebrates is widespread and not restricted to classical clock structures. The expression of the Clock gene in zebrafish shows a strong circadian oscillation in many tissues in vivo and in culture, showing that endogenous oscillators exist in peripheral organs. A defining feature of ci...
Light acts directly on organs and cells in culture to set the vertebrate circadian clock.
{"1011": 0.12986256182193756, "1047": 1.2742929458618164, "1052": 0.045809537172317505, "2003": 0.1401015669107437, "2005": 0.04953393340110779, "2006": 0.8004589080810547, "2007": 0.1693800985813141, "2011": 0.5069117546081543, "2029": 0.09672962874174118, "2063": 0.7426811456680298, "2073": 0.07159364968538284, "2076...
4320424
The KRAS oncogene product is considered a major target in anticancer drug discovery. However, direct interference with KRAS signalling has not yet led to clinically useful drugs. Correct localization and signalling by farnesylated KRAS is regulated by the prenyl-binding protein PDEδ, which sustains the spatial organiza...
Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling
{"1049": 0.44753631949424744, "1055": 0.10379679501056671, "1060": 0.9194108247756958, "1997": 0.052318159490823746, "2005": 0.1994270235300064, "2011": 0.0770333781838417, "2012": 0.14349138736724854, "2026": 0.9248477816581726, "2028": 0.255429208278656, "2029": 0.04674193635582924, "2033": 0.49982786178588867, "2037...
4321295
Cooperation among individuals is necessary for evolutionary transitions to higher levels of biological organization. In such transitions, groups of individuals at one level (such as single cells) cooperate to form selective units at a higher level (such as multicellular organisms). Though the evolution of cooperation i...
Evolution of novel cooperative swarming in the bacterium Myxococcus xanthus
{"1011": 0.18411032855510712, "1017": 0.004870930220931768, "1043": 1.035461664199829, "1996": 0.15693697333335876, "1997": 0.16607704758644104, "1999": 0.03925827145576477, "2002": 0.6624060273170471, "2003": 0.39893341064453125, "2004": 0.010684899985790253, "2008": 0.10467668622732162, "2011": 0.1485546976327896, "2...
4321947
Glucagon is a 29-amino acid pancreatic hormone which counteracts the blood glucose-lowering action of insulin by stimulating hepatic glycogenolysis and gluconeogenesis1. The structure of the hamster pancreatic glucagon precursor has recently been determined from the sequence of a cloned cDNA2. Hamster preproglucagon is...
Exon duplication and divergence in the human preproglucagon gene
{"1011": 0.4879087805747986, "1015": 0.026025565341114998, "1016": 0.8877626657485962, "1038": 0.9724938273429871, "1042": 0.36900100111961365, "1043": 0.3560888469219208, "1048": 0.1889725625514984, "1056": 0.053244512528181076, "1157": 0.2969166338443756, "2004": 0.18573370575904846, "2006": 0.46608972549438477, "200...
4323425
BCL-2 was isolated from the t(14;18) chromosomal breakpoint in follicular B-cell lymphoma1–3. Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths4–13. An emerging family of Bcl-2 -related proteins share two highly conserved regions14–20 referred to here as Bcl-2 ho...
BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax
{"1011": 0.11778303235769272, "1015": 0.3177432417869568, "1019": 0.2317005842924118, "1023": 0.016465263441205025, "1047": 0.40806588530540466, "1048": 0.04860413447022438, "1999": 0.043007105588912964, "2008": 0.06154331564903259, "2010": 0.9348671436309814, "2011": 0.2983669638633728, "2013": 0.34370049834251404, "2...
4323449
More than forty per cent of the mammalian genome is derived from retroelements, of which about one-quarter are endogenous retroviruses (ERVs). Some are still active, notably in mice the highly polymorphic early transposon (ETn)/MusD and intracisternal A-type particles (IAP). ERVs are transcriptionally silenced during e...
KAP1 controls endogenous retroviruses in embryonic stem cells
{"1011": 0.12038381397724152, "1015": 0.1064341589808464, "1016": 0.03360854089260101, "1017": 0.10026945173740387, "1036": 0.32905077934265137, "1038": 0.40089741349220276, "1043": 0.6441128253936768, "1050": 0.0913962796330452, "1996": 0.29328158497810364, "1998": 0.026976587250828743, "1999": 0.0009760859538801014, ...
4324278
The rapamycin-sensitive TOR signalling pathway in Saccharomyces cerevisiae activates a cell-growth program in response to nutrients such as nitrogen and carbon. The TOR1 and TOR2 kinases (TOR) control cytoplasmic protein synthesis and degradation through the conserved TAP42 protein. Upon phosphorylation by TOR, TAP42 b...
The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors.
{"1015": 0.10731173306703568, "1017": 0.013579257763922215, "1023": 0.3554046154022217, "1040": 0.10291612148284912, "1041": 0.6999598741531372, "2003": 0.1994270235300064, "2005": 0.11691460013389587, "2011": 0.16110190749168396, "2013": 0.45437926054000854, "2024": 0.4067663550376892, "2029": 0.004870930220931768, "2...
4325137
Murine embryonic stem (ES) cells are pluripotent cell lines established directly from the early embryo1,2 which can contribute differentiated progeny to all adult tissues, including the germ-cell lineage3, after re-incorporation into the normal embryo. They provide both a cellular vector for the generation of transgeni...
Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides
{"1020": 0.10555581003427505, "1045": 0.055094651877880096, "1047": 0.34508460760116577, "1056": 0.28082266449928284, "1062": 0.4041621685028076, "2003": 0.18492233753204346, "2029": 0.020300358533859253, "2047": 0.1946154683828354, "2050": 0.38441169261932373, "2057": 0.06612417846918106, "2061": 0.6639154553413391, "...
4325398
Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative...
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
{"1011": 0.06154331564903259, "1155": 0.680370569229126, "2002": 0.8212929964065552, "2011": 0.20739519596099854, "2029": 0.026976587250828743, "2064": 0.02792670577764511, "2067": 0.012615402229130268, "2075": 0.6613984704017639, "2089": 0.12470348179340363, "2091": 0.3683255612850189, "2128": 0.38441169261932373, "22...
4326318
The decline of tissue regenerative potential is a hallmark of ageing and may be due to age-related changes in tissue-specific stem cells. A decline in skeletal muscle stem cell (satellite cell) activity due to a loss of Notch signalling results in impaired regeneration of aged muscle. The decline in hepatic progenitor ...
Rejuvenation of aged progenitor cells by exposure to a young systemic environment
{"1041": 0.11430477350950241, "1044": 0.10555581003427505, "1998": 0.12384103983640671, "2001": 0.026025565341114998, "2004": 0.40546512603759766, "2011": 0.30989447236061096, "2013": 0.6011518239974976, "2029": 0.16359257698059082, "2033": 0.5444341897964478, "2034": 0.6223390698432922, "2064": 0.30558720231056213, "2...
4335423
Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown. Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial–haematopoietic precursors or haemogenic endothelial cells remains controversial. Proxim...
Continuous single-cell imaging of blood generation from haemogenic endothelium
{"1011": 0.11430477350950241, "1017": 0.24859806895256042, "1047": 0.06703783571720123, "1060": 0.8699195384979248, "2008": 0.09495500475168228, "2013": 0.5162794589996338, "2029": 0.30486753582954407, "2031": 0.151916041970253, "2038": 0.11778303235769272, "2046": 0.38441169261932373, "2058": 0.022212404757738113, "20...
4335599
The recent availability in culture of embryo-derived pluripotential cells which exhibit both a normal karyotype and a high differentiative ability1–3 has encouraged us to assess the potential of these cells to form functional germ cells following their incorporation into chimaeric mice. We report here the results of bl...
Formation of germ-line chimaeras from embryo-derived teratocarcinoma cell lines
{"1011": 0.12642613053321838, "1020": 0.06795065850019455, "1022": 0.11430477350950241, "1023": 0.10818854719400406, "1039": 0.8649974465370178, "1041": 0.4374985992908478, "1043": 0.3615458607673645, "1052": 0.6970458030700684, "1053": 0.14349138736724854, "2005": 0.09495500475168228, "2008": 0.0009760859538801014, "2...
4336849
CHLOROQUINE is thought to act against falciparum malaria by accumulating in the acid vesicles of the parasite and interfering with their function1–4. Parasites resistant to chloroquine expel the drug rapidly in an unaltered form, thereby reducing levels of accumulation in the vesicles5. The discovery that verapamil par...
Chloroquine resistance not linked to mdr-like genes in a Plasmodium falciparum cross
{"1011": 0.056018441915512085, "1015": 0.3850763738155365, "1039": 0.17267228662967682, "1996": 0.07884006202220917, "2000": 0.08961215615272522, "2003": 0.00875066313892603, "2008": 0.11951763927936554, "2011": 0.12038381397724152, "2013": 0.2018241584300995, "2028": 0.053244512528181076, "2029": 0.09228714555501938, ...
4340358
The cellular and molecular mechanisms that enable us to sense cold are not well understood. Insights into this process have come from the use of pharmacological agents, such as menthol, that elicit a cooling sensation. Here we have characterized and cloned a menthol receptor from trigeminal sensory neurons that is also...
Identification of a cold receptor reveals a general role for TRP channels in thermosensation
{"1011": 0.29981520771980286, "1041": 0.7546905279159546, "1050": 0.848413348197937, "1996": 0.10467668622732162, "1997": 0.053244512528181076, "2007": 0.04113444685935974, "2029": 0.24018502235412598, "2037": 0.151916041970253, "2075": 0.5551415085792542, "2078": 0.029824240133166313, "2079": 0.28743788599967957, "209...
4340509
Pattern formation of biological structures involves organizing different types of cells into a spatial configuration. In this study, we investigate the physical basis of biological patterning of the Drosophila retina in vivo. We demonstrate that E- and N-cadherins mediate apical adhesion between retina epithelial cells...
Surface mechanics mediate pattern formation in the developing retina
{"1996": 0.3012613356113434, "1998": 0.06429435312747955, "1999": 0.01934296265244484, "2004": 0.15442965924739838, "2011": 0.03925827145576477, "2029": 0.3084607720375061, "2046": 0.3883931338787079, "2060": 0.2089812457561493, "2073": 0.2447827309370041, "2076": 0.1994270235300064, "2077": 0.6389714479446411, "2079":...
4343437
Drosophila neuroblasts and epithelial cells in the procephalic neurogenic region divide perpendicular to the surface, and segregate the proteins Numb and Prospero into the basal daughter cell. We demonstrate here that orientation of the mitotic spindle and correct localization of Numb and Prospero in these cells requir...
Role of inscuteable in orienting asymmetric cell divisions in Drosophila
{"1011": 0.055094651877880096, "1039": 0.7182208299636841, "1040": 0.2852376699447632, "1041": 0.42735910415649414, "1999": 0.11604541540145874, "2006": 0.18167030811309814, "2008": 0.11256109178066254, "2011": 0.27934664487838745, "2015": 0.2607102394104004, "2029": 0.026976587250828743, "2037": 0.012615402229130268, ...
4343811
A genetic interference phenomenon in the nematode Caenorhabditis elegans has been described in which expression of an individual gene can be specifically reduced by microinjecting a corresponding fragment of double-stranded (ds) RNA. One striking feature of this process is a spreading effect: interference in a broad re...
Specific interference by ingested dsRNA.
{"1011": 0.06154331564903259, "1015": 0.37102460861206055, "1017": 0.07884006202220917, "1018": 0.10467668622732162, "1020": 0.4673144817352295, "1048": 0.3963087201118469, "1050": 0.6921701431274414, "1054": 0.2830325961112976, "1155": 0.4425300657749176, "1164": 0.4228905141353607, "1999": 0.5191890001296997, "2004":...
4345315
Missense mutations in the CIAS1 gene cause three autoinflammatory disorders: familial cold autoinflammatory syndrome, Muckle–Wells syndrome and neonatal-onset multiple-system inflammatory disease. Cryopyrin (also called Nalp3), the product of CIAS1, is a member of the NOD-LRR protein family that has been linked to the ...
Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3
{"1018": 0.2470736801624298, "1043": 0.35813871026039124, "1054": 0.03360854089260101, "1157": 0.08871890604496002, "2003": 0.3141832649707794, "2009": 0.0317181795835495, "2011": 0.32058215141296387, "2029": 0.043007105588912964, "2049": 0.004870930220931768, "2054": 0.2667117714881897, "2058": 0.13243216276168823, "2...
4345605
Schizophrenia is a complex disorder that interferes with the function of several brain systems required for cognition and normal social behaviour. Although the most notable clinical aspects of the disease only become apparent during late adolescence or early adulthood, many lines of evidence suggest that schizophrenia ...
Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling
{"1049": 0.22157983481884003, "1997": 0.055094651877880096, "1998": 0.0317181795835495, "2003": 0.1913948506116867, "2004": 0.15860503911972046, "2022": 0.043007105588912964, "2054": 0.4914994537830353, "2057": 0.10993985831737518, "2058": 0.6096806526184082, "2061": 0.37304413318634033, "2085": 0.554580807685852, "208...
4345757
Obesity is now so common within the world's population that it is beginning to replace undernutrition and infectious diseases as the most significant contributor to ill health. In particular, obesity is associated with diabetes mellitus, coronary heart disease, certain forms of cancer, and sleep-breathing disorders. Ob...
Obesity as a medical problem.
{"1997": 0.08064348995685577, "2001": 0.1401015669107437, "2003": 0.0058422754518687725, "2013": 0.2089812457561493, "2015": 0.11778303235769272, "2034": 0.083342544734478, "2042": 0.21687394380569458, "2043": 0.2034190446138382, "2070": 0.10026945173740387, "2075": 0.1221139207482338, "2081": 0.35128939151763916, "210...
4346436
Unlike most synthetic materials, biological materials often stiffen as they are deformed. This nonlinear elastic response, critical for the physiological function of some tissues, has been documented since at least the 19th century, but the molecular structure and the design principles responsible for it are unknown. C...
Nonlinear Elasticity in Biological Gels
{"1011": 0.15943801403045654, "1996": 0.012615402229130268, "1997": 0.05139094591140747, "2011": 0.08064348995685577, "2019": 0.10026945173740387, "2025": 0.5827828645706177, "2033": 0.7009293437004089, "2034": 0.24859806895256042, "2057": 0.401551216840744, "2058": 0.3409265875816345, "2075": 0.7115318179130554, "2079...
4346731
The development and maintenance of an epithelium requires finely balanced rates of growth and cell death. However, the mechanical and biochemical mechanisms that ensure proper feedback control of tissue growth, which when deregulated contribute to tumorigenesis, are poorly understood. Here we use the fly notum as a mod...
Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding
{"1011": 0.05139094591140747, "1017": 0.3554046154022217, "1038": 0.2689530849456787, "1043": 0.27786844968795776, "1048": 0.07341018319129944, "1056": 0.0174254160374403, "1058": 0.15860503911972046, "1999": 0.32270604372024536, "2008": 0.08154398202896118, "2011": 0.32341301441192627, "2029": 0.1485546976327896, "203...
4347374
Viral replication usually requires that innate intracellular lines of defence be overcome, a task usually accomplished by specialized viral gene products. The virion infectivity factor (Vif) protein of human immunodeficiency virus (HIV) is required during the late stages of viral production to counter the antiviral act...
Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts
{"1041": 0.48670899868011475, "2004": 0.45623743534088135, "2011": 0.3241194784641266, "2029": 0.007782140281051397, "2048": 0.1485546976327896, "2063": 0.32129061222076416, "2075": 0.4450363218784332, "2076": 0.48850810527801514, "2079": 0.1619328260421753, "2090": 0.11168810725212097, "2135": 0.1401015669107437, "215...
4350400
Dynamically polarized membrane proteins define different cell boundaries and have an important role in intercellular communication—a vital feature of multicellular development. Efflux carriers for the signalling molecule auxin from the PIN family are landmarks of cell polarity in plants and have a crucial involvement i...
Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions
{"1005": 0.10993985831737518, "1011": 0.04207121208310127, "1013": 0.5562619566917419, "1048": 0.2539152204990387, "1051": 0.10026945173740387, "2012": 0.3443928062915802, "2029": 0.2145126610994339, "2058": 0.2976420819759369, "2078": 0.058784693479537964, "2079": 0.17431432008743286, "2098": 0.24248650670051575, "215...
4353857
The extreme obesity of the obese (ob/ob) mouse is attributable to mutations in the gene encoding leptin, an adipocyte-specific secreted protein which has profound effects on appetite and energy expenditure. We know of no equivalent evidence regarding leptin's role in the control of fat mass in humans. We have examined ...
Congenital leptin deficiency is associated with severe early-onset obesity in humans.
{"1011": 0.6170841455459595, "1017": 0.129004567861557, "1038": 0.25694093108177185, "1039": 0.04207121208310127, "1043": 0.3662964701652527, "1048": 0.3683255612850189, "1155": 0.35060185194015503, "1156": 1.3295379877090454, "1996": 0.0058422754518687725, "1997": 0.053244512528181076, "2003": 0.10993985831737518, "20...
4361990
PROGRESSIVE cerebral deposition of the amyloid β-peptide is an early and invariant feature of Alzheimer's disease. The β-peptide is released by proteolytic cleavages from the β-amyloid precursor protein (βAPP)1, a membrane-spanning glycoprotein expressed in most mammalian cells. Normal secretion of βAPP involves a clea...
Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments
{"1017": 0.15359249711036682, "1047": 0.23015019297599792, "1996": 0.12642613053321838, "1998": 0.0038986403960734606, "2011": 0.1930064558982849, "2029": 0.176772341132164, "2048": 0.0019512200960889459, "2076": 0.15359249711036682, "2078": 0.37371641397476196, "2079": 0.22626367211341858, "2099": 0.09761575609445572,...
4362729
Cell growth, an increase in mass and size, is a highly regulated cellular event. The Akt/mTOR (mammalian target of rapamycin) signalling pathway has a central role in the control of protein synthesis and thus the growth of cells, tissues and organisms. A striking example of a physiological context requiring rapid cell ...
A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth
{"1011": 0.4556184411048889, "1013": 0.24018502235412598, "1017": 0.7220231294631958, "1019": 0.08871890604496002, "1038": 0.8608771562576294, "1042": 0.2026219218969345, "1044": 0.8161250352859497, "1050": 0.1677299439907074, "1060": 0.21687394380569458, "1155": 0.8567397594451904, "1156": 0.9635916948318481, "1996": ...
4363526
The three-dimensional structure of an HNF-3/fork head DNA-recognition motif complexed with DNA has been determined by X-ray crystallography at 2.5 Å resolution. This α/β protein binds B-DNA as a monomer, through interactions with the DNA backbone and through both direct and water-mediated major and minor groove base co...
Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5
{"1011": 0.0317181795835495, "1017": 0.12384103983640671, "1039": 0.24248650670051575, "2003": 0.12470348179340363, "2007": 0.1212492436170578, "2011": 0.006812678650021553, "2015": 0.18492233753204346, "2019": 0.4926934838294983, "2033": 0.7201237678527832, "2043": 0.04953393340110779, "2048": 0.2786078155040741, "206...
4364884
Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes. However, a direct mechanistic link between extra centrosomes and CIN has not been established. It has been proposed that extra centrosomes generate CIN by promoting multipolar anaphase, a highly abnormal d...
A Mechanism Linking Extra Centrosomes to Chromosomal Instability
{"1011": 0.058784693479537964, "1039": 0.7647408246994019, "1048": 0.43244171142578125, "1051": 0.037378571927547455, "1060": 0.2447827309370041, "1999": 0.037378571927547455, "2011": 0.32270604372024536, "2013": 0.3012613356113434, "2025": 0.08064348995685577, "2026": 0.623910129070282, "2029": 0.255429208278656, "203...
4366738
Although haematopoietic stem cells (HSCs) are commonly assumed to reside within a specialized microenvironment, or niche, most published experimental manipulations of the HSC niche have affected the function of diverse restricted progenitors. This raises the fundamental question of whether HSCs and restricted progenito...
Haematopoietic stem cells and early lymphoid progenitors occupy distinct bone marrow niches
{"1011": 0.021256839856505394, "1018": 0.045809537172317505, "1023": 0.10379679501056671, "1043": 0.3656192123889923, "2003": 0.04674193635582924, "2005": 0.21135559678077698, "2008": 0.05139094591140747, "2012": 0.1011524572968483, "2013": 0.29400965571403503, "2015": 0.02316705882549286, "2024": 0.0797421783208847, "...
4373433
Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses an...
Broad neutralization coverage of HIV by multiple highly potent antibodies
{"1011": 0.1685553640127182, "1015": 0.4734157919883728, "1017": 0.2607102394104004, "1043": 0.2026219218969345, "1054": 0.9394577741622925, "1996": 0.22079704701900482, "1998": 0.20739519596099854, "2007": 0.1873544454574585, "2008": 0.1693800985813141, "2012": 0.4248080551624298, "2028": 0.23556606471538544, "2029": ...
4373445
The GTPases Rac1, RhoA and Cdc42 act together to control cytoskeleton dynamics. Recent biosensor studies have shown that all three GTPases are activated at the front of migrating cells, and biochemical evidence suggests that they may regulate one another: Cdc42 can activate Rac1 (ref. 8), and Rac1 and RhoA are mutually...
Coordination of Rho GTPase activities during cell protrusion
{"1041": 0.9021284580230713, "1048": 0.45251765847206116, "1053": 0.33675122261047363, "2000": 0.037378571927547455, "2005": 0.15442965924739838, "2008": 0.19220098853111267, "2011": 0.12556517124176025, "2013": 0.3381449282169342, "2015": 0.23864774405956268, "2029": 0.1693800985813141, "2035": 0.7067264318466187, "20...
4378885
Understanding the genetic mechanisms underlying natural variation in gene expression is a central goal of both medical and evolutionary genetics, and studies of expression quantitative trait loci (eQTLs) have become an important tool for achieving this goal. Although all eQTL studies so far have assayed messenger RNA l...
Understanding mechanisms underlying human gene expression variation with RNA sequencing
{"1009": 0.623910129070282, "1011": 0.08692999184131622, "1156": 0.33953672647476196, "1996": 0.10818854719400406, "1999": 0.06520967930555344, "2015": 0.619189441204071, "2029": 0.13670019805431366, "2033": 0.6950984001159668, "2048": 0.28597161173820496, "2061": 0.638455867767334, "2064": 0.009718249551951885, "2073"...
4380004
The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Ne...
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
{"1056": 0.8433839678764343, "2003": 0.12642613053321838, "2011": 0.2983669638633728, "2012": 0.6223390698432922, "2015": 0.037378571927547455, "2033": 0.5010119676589966, "2035": 0.20501139760017395, "2043": 0.022212404757738113, "2044": 0.4709797203540802, "2063": 0.33115679025650024, "2076": 0.026025565341114998, "2...
4380287
Immune homeostasis in tissues is achieved through a delicate balance between pathogenic T-cell responses directed at tissue-specific antigens and the ability of the tissue to inhibit these responses. The mechanisms by which tissues and the immune system communicate to establish and maintain immune homeostasis are curre...
Response to self antigen imprints regulatory memory in tissues
{"1047": 0.3554046154022217, "2003": 0.1677299439907074, "2008": 0.12384103983640671, "2011": 0.1994270235300064, "2013": 0.15359249711036682, "2015": 0.8332487344741821, "2024": 0.29981520771980286, "2026": 0.567397952079773, "2029": 0.1602703034877777, "2035": 0.37371641397476196, "2054": 0.10203468054533005, "2064":...
4380451
Pluripotency pertains to the cells of early embryos that can generate all of the tissues in the organism. Embryonic stem cells are embryo-derived cell lines that retain pluripotency and represent invaluable tools for research into the mechanisms of tissue formation. Recently, murine fibroblasts have been reprogrammed d...
Reprogramming of human somatic cells to pluripotency with defined factors
{"1011": 0.1229778528213501, "1014": 0.5151132941246033, "1018": 0.1384023278951645, "1019": 0.42416930198669434, "1020": 0.03360854089260101, "2004": 0.5849615335464478, "2011": 0.14349138736724854, "2024": 0.11430477350950241, "2025": 0.15359249711036682, "2037": 0.07793712615966797, "2042": 0.09317722171545029, "204...
4381486
Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older (‘immortal’) DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells. Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridin...
Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU
{"100": 0.5174443125724792, "2005": 0.17840765416622162, "2011": 0.33605360984802246, "2024": 0.029824240133166313, "2025": 0.43623676896095276, "2029": 0.07884006202220917, "2035": 0.176772341132164, "2042": 0.07341018319129944, "2051": 0.6363908052444458, "2053": 0.3423145115375519, "2054": 0.04860413447022438, "2057...
4385779
Circadian (∼24 hour) clocks are fundamentally important for coordinated physiology in organisms as diverse as cyanobacteria and humans. All current models of the molecular circadian clockwork in eukaryotic cells are based on transcription-translation feedback loops. Non-transcriptional mechanisms in the clockwork have ...
Circadian Clocks in Human Red Blood Cells
{"1011": 0.3269403576850891, "1022": 0.23787821829319, "1038": 0.34577593207359314, "1043": 0.5662899017333984, "1044": 0.53589928150177, "1046": 0.2026219218969345, "1047": 0.6107416749000549, "1052": 0.25467249751091003, "1055": 0.5562619566917419, "1058": 0.0770333781838417, "2003": 0.2652147710323334, "2006": 0.216...
4387484
The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Kap...
G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator.
{"1011": 0.10291612148284912, "1017": 0.1401015669107437, "1020": 0.23479416966438293, "1040": 0.11517547070980072, "1043": 0.07793712615966797, "1044": 0.04674193635582924, "1046": 0.6487176418304443, "1047": 0.6989894509315491, "1048": 0.26296505331993103, "1049": 0.23864774405956268, "1053": 0.4909018874168396, "106...
4387494
PURPOSE Acute myeloid leukemia (AML) is a heterogeneous disease with poor outcomes. Despite increased evidence shows that dysregulation of histone modification contributes to AML, specific drugs targeting key histone modulators are not applied in the clinical treatment of AML. Here, we investigated whether targeting KD...
Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for acute myeloid leukemia
{"1011": 0.2034190446138382, "1014": 0.12038381397724152, "1017": 0.026025565341114998, "1020": 0.25694093108177185, "1044": 0.3019835948944092, "1052": 0.7276995778083801, "1057": 0.30558720231056213, "1996": 0.3191637098789215, "1997": 0.23402166366577148, "1999": 0.10291612148284912, "2002": 0.9147270321846008, "200...
4387784
Half the world's population is chronically infected with Helicobacter pylori, causing gastritis, gastric ulcers and an increased incidence of gastric adenocarcinoma. Its proton-gated inner-membrane urea channel, HpUreI, is essential for survival in the acidic environment of the stomach. The channel is closed at neutral...
Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori
{"1011": 0.26446542143821716, "1040": 0.08692999184131622, "1042": 0.8074519634246826, "1051": 1.0478670597076416, "1996": 0.4002431631088257, "1997": 0.05046287178993225, "1999": 0.1946154683828354, "2007": 0.36967599391937256, "2011": 0.31132611632347107, "2012": 0.15023678541183472, "2029": 0.22079704701900482, "203...
4388082
In a Drosophila follicle the oocyte always occupies a posterior position among a group of sixteen germline cells. Although the importance of this cell arrangement for the subsequent formation of the anterior-posterior axis of the embryo is well documented, the molecular mechanism responsible for the posterior localizat...
Drosophila oocyte localization is mediated by differential cadherin-based adhesion.
{"1011": 0.025073638185858727, "1017": 0.2034190446138382, "1037": 0.02316705882549286, "1043": 0.6704301834106445, "2013": 0.1946154683828354, "2015": 0.2018241584300995, "2020": 0.13414156436920166, "2031": 0.25239890813827515, "2033": 0.5584990978240967, "2035": 0.17020416259765625, "2038": 0.010684899985790253, "20...
4388470
In the mammalian model of sex determination, embryos are considered to be sexually indifferent until the transient action of a sex-determining gene initiates gonadal differentiation. Although this model is thought to apply to all vertebrates, this has yet to be established. Here we have examined three lateral gynandrom...
Somatic sex identity is cell-autonomous in the chicken
{"1039": 0.259204238653183, "1048": 0.8366385698318481, "1056": 1.0087559223175049, "1996": 0.17020416259765625, "2005": 0.016465263441205025, "2008": 0.0174254160374403, "2011": 0.3297532796859741, "2012": 0.3995884954929352, "2013": 0.11517547070980072, "2029": 0.11430477350950241, "2073": 0.0913962796330452, "2076":...
4389252
Cytotoxic T lymphocytes (CTLs) destroy virally infected and tumorigenic cells by releasing the contents of specialized secretory lysosomes—termed ‘lytic granules’—at the immunological synapse formed between the CTL and the target. On contact with the target cell, the microtubule organizing centre of the CTL polarizes t...
Centrosome polarization delivers secretory granules to the immunological synapse
{"1011": 0.06337817758321762, "1052": 1.176850438117981, "1057": 0.7845434546470642, "2003": 0.2954642176628113, "2004": 0.03266380727291107, "2008": 0.14433705806732178, "2011": 0.3283478021621704, "2012": 0.1358480453491211, "2014": 0.9531047344207764, "2029": 0.2026219218969345, "2099": 0.2018241584300995, "2121": 0...
4389394
The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization of p53 is crucial for its tumour suppressor function. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is no...
Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization
{"1009": 0.3248254358768463, "1011": 0.22626367211341858, "1039": 1.0519683361053467, "1043": 0.24171993136405945, "1056": 0.8408597707748413, "1058": 0.2160874605178833, "1155": 0.40351006388664246, "1157": 0.6064908504486084, "1525": 0.07159364968538284, "2001": 0.08782484382390976, "2004": 0.2689530849456787, "2011"...
4391121
Half a century ago, chronic granulomatous disease (CGD) was first described as a disease fatally affecting the ability of children to survive infections. Various milestone discoveries have since been made, from an insufficient ability of patients’ leucocytes to kill microbes to the underlying genetic abnormalities. In ...
Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease
{"1996": 0.07068414986133575, "2002": 0.8957691192626953, "2004": 0.3381449282169342, "2011": 0.014542185701429844, "2064": 0.034552380442619324, "2129": 0.20102575421333313, "2182": 0.1477125883102417, "2239": 0.3077431619167328, "2265": 0.052318159490823746, "2339": 0.3141832649707794, "2368": 0.37907835841178894, "2...
4391685
The architecture and adhesiveness of a cell microenvironment is a critical factor for the regulation of spindle orientation in vivo. Using a combination of theory and experiments, we have investigated spindle orientation in HeLa (human) cells. Here we show that spindle orientation can be understood as the result of the...
Experimental and theoretical study of mitotic spindle orientation
{"2003": 0.2696990668773651, "2013": 0.010684899985790253, "2015": 0.09850110858678818, "2028": 0.23402166366577148, "2038": 0.1229778528213501, "2047": 0.4734157919883728, "2064": 0.1970241367816925, "2071": 0.3519764244556427, "2072": 0.5517725944519043, "2083": 0.19782574474811554, "2094": 0.05694137513637543, "2124...
4391817
Genome sequencing has uncovered a new mutational phenomenon in cancer and congenital disorders called chromothripsis. Chromothripsis is characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes. The mechanism for chromoth...
CHROMOTHRIPSIS FROM DNA DAMAGE IN MICRONUCLEI
{"1011": 0.20102575421333313, "1045": 0.0913962796330452, "1048": 0.9379299283027649, "1049": 0.08064348995685577, "1997": 0.25088030099868774, "1998": 0.021256839856505394, "1999": 0.00875066313892603, "2003": 0.12642613053321838, "2011": 0.3318578004837036, "2015": 0.083342544734478, "2024": 0.007782140281051397, "20...
4392608
Methylation of cytosines is an essential epigenetic modification in mammalian genomes, yet the rules that govern methylation patterns remain largely elusive. To gain insights into this process, we generated base-pair-resolution mouse methylomes in stem cells and neuronal progenitors. Advanced quantitative analysis iden...
DNA-binding factors shape the mouse methylome at distal regulatory regions
{"1011": 0.1873544454574585, "1016": 0.8500841856002808, "1052": 0.5876781344413757, "1056": 0.32764431834220886, "1999": 0.004870930220931768, "2002": 0.38905516266822815, "2005": 0.11951763927936554, "2007": 0.24554696679115295, "2008": 0.1734936386346817, "2011": 0.46055975556373596, "2012": 0.12814582884311676, "20...
4393153
RNA polymerase (Pol) II catalyses DNA-dependent RNA synthesis during gene transcription. There is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated ...
Molecular basis of RNA-dependent RNA polymerase II activity
{"1038": 0.2800849378108978, "1048": 0.3622259199619293, "1056": 0.4512746334075928, "1155": 0.12986256182193756, "1999": 0.13243216276168823, "2003": 0.022212404757738113, "2011": 0.3982778787612915, "2015": 0.1873544454574585, "2024": 0.22001366317272186, "2026": 0.3850763738155365, "2053": 1.0409941673278809, "2076"...
4394525
Nociceptor sensory neurons are specialized to detect potentially damaging stimuli, protecting the organism by initiating the sensation of pain and eliciting defensive behaviours. Bacterial infections produce pain by unknown molecular mechanisms, although they are presumed to be secondary to immune activation. Here we d...
Bacteria activate sensory neurons that modulate pain and inflammation
{"1011": 0.3084607720375061, "1015": 0.021256839856505394, "1016": 0.4537591338157654, "1017": 0.5021947622299194, "1041": 0.8845420479774475, "1042": 0.06612417846918106, "1055": 0.8306987881660461, "1996": 0.2539152204990387, "1999": 0.12470348179340363, "2004": 0.12642613053321838, "2005": 0.06612417846918106, "2007...
4394817
In the established model of mammalian cell cycle control, the retinoblastoma protein (Rb) functions to restrict cells from entering S phase by binding and sequestering E2f activators (E2f1, E2f2 and E2f3), which are invariably portrayed as the ultimate effectors of a transcriptional program that commit cells to enter a...
E2F1-3 Switch from Activators in Progenitor Cells to Repressors in Differentiating Cells
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4396105
Somatic mutations in the small GTPase K-Ras are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Efforts to target this oncogene directly have faced difficulties owing to its picomolar affinity for GTP/GDP and the absence of known allosteri...
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
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4398832
The most conspicuous event in the cell cycle is the alignment of chromosomes in metaphase. Chromosome alignment fosters faithful segregation through the formation of bi-oriented attachments of kinetochores to spindle microtubules. Notably, numerous kinetochore-microtubule (k-MT) attachment errors are present in early m...
Cyclin A Regulates Kinetochore-Microtubules to Promote Faithful Chromosome Segregation