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10.1073/pnas.0802430105 | 122,686,997 | In the Earth's history, periods of relatively stable climate have often been interrupted by sharp transitions to a contrasting state. One explanation for such events of abrupt change is that they happened when the earth system reached a critical tipping point. However, this remains hard to prove for events in the remot... | 10.1038/s41586-021-03263-2 | This paper presents evidence of tipping points in palaeoclimate records |
10.1073/pnas.1511451112 | 103,646,668 | Abrupt transitions of regional climate in response to the gradual rise in atmospheric greenhouse gas concentrations are notoriously difficult to foresee. However, such events could be particularly challenging in view of the capacity required for society and ecosystems to adapt to them. We present, to our knowledge, the... | 10.1038/s41586-021-03263-2 | This study illustrates that tipping points are found in future projections with complex Earth system models |
10.1073/pnas.1810141115 | 62,611,647 | We explore the risk that self-reinforcing feedbacks could push the Earth System toward a planetary threshold that, if crossed, could prevent stabilization of the climate at intermediate temperature rises and cause continued warming on a “Hothouse Earth” pathway even as human emissions are reduced. Crossing the threshol... | 10.1038/s41586-021-03263-2 | This paper estimates tipping point thresholds (we use its central estimates here) |
10.1098/rspa.2018.0504 | 96,362,723 | A classical scenario for tipping is that a dynamical system experiences a slow parameter drift across a fold tipping point, caused by a run-away positive feedback loop. We study what happens if one turns around after one has crossed the threshold. We derive a simple criterion that relates how far the parameter exceeds ... | 10.1038/s41586-021-03263-2 | This study describes the mathematical theory for how much and how long a tipping point threshold can be exceeded without causing tipping |
10.5194/esd-8-617-2017 | 109,416,577 | Abstract. The meeting of the United Nations Framework Convention on Climate Change (UNFCCC) in December 2015 committed parties at the convention to hold the rise in global average temperature to well below 2.0 °C above pre-industrial levels. It also committed the parties to pursue efforts to limit warming to 1.5 °C. Th... | 10.1038/s41586-021-03263-2 | This article defines the temperature overshoot profiles used in this study |
10.2337/dc18-s015 | 41,677,453 | The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Com... | 10.1038/s41574-018-0122-1 | 2018 Current guideline of the American Diabetes Association for the diagnosis and treatment of diabetes mellitus |
10.1002/oby.20351 | 40,151,273 | Abstract Objective: Despite the extended overnight fast, paradoxically, people are typically not ravenous in the morning and breakfast is typically the smallest meal of the day. We assessed whether this paradox could be explained by an endogenous circadian influence on appetite with a morning trough, while controlling ... | 10.1038/s41574-018-0122-1 | First study showing the control of human appetite by the endogenous circadian timing system |
10.1073/pnas.0806717105 | 104,291,977 | Mammals have circadian clocks in peripheral tissues, but there is no direct evidence of their physiological importance. Unlike the suprachiasmatic nucleus clock that is set by light and drives rest–activity and fasting–feeding cycles, peripheral clocks are set by daily feeding, suggesting that at least some contribute ... | 10.1038/s41574-018-0122-1 | Key study showing that the hepatic clock is essential to maintain euglycemia during the fasting period in mice |
10.1111/dom.12616 | 41,027,715 | Aim To determine the impact of a functional human islet clock on insulin secretion and gene transcription. Methods Efficient circadian clock disruption was achieved in human pancreatic islet cells by small interfering RNA ‐mediated knockdown of CLOCK . Human islet secretory function was assessed in the presence or abse... | 10.1038/s41574-018-0122-1 | Study demonstrating that CLOCK inhibition with small interfering RNA disrupts insulin secretion in cultured human pancreatic islet cells |
10.1126/science.1108750 | 20,760,996 | The CLOCK transcription factor is a key component of the molecular circadian clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding rhythm, are hyperphagic and obese, and develop a metabolic syndrome of hyperleptin... | 10.1038/s41574-018-0122-1 | First study to show metabolic disease in a clock gene knockout mouse |
10.1073/pnas.0808180106 | 20,849,944 | There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined ... | 10.1038/s41574-018-0122-1 | First study demonstrating that humans develop reduced glucose tolerance when subjected to conditions of circadian misalignment |
10.1073/pnas.0703247104 | 82,827,541 | Many aspects of physiology and behavior follow a circadian rhythm. Brain and muscle Arnt-like protein-1 ( BMAL1 ) is a key component of the mammalian molecular clock, which controls circadian oscillations. In the rat, the gene encoding Bmal1 is located within hypertension susceptibility loci. We analyzed the SNP distri... | 10.1038/s41574-018-0122-1 | First study showing an association between a clock gene single nucleotide polymorphism and type 2 diabetes mellitus |
10.2337/db10-1098 | 18,594,214 | OBJECTIVE Previous animal studies suggest a functional relationship between metabolism, type 2 diabetes, and the amplitude of daily rhythms in white adipose tissue (WAT). However, data interpretation is confounded by differences in genetic background and diet or limited sampling points. We have taken the novel approach... | 10.1038/s41574-018-0122-1 | First study comparing in vivo clock gene expression rhythms between healthy participants, participants with obesity and patients with type 2 diabetes mellitus |
10.2337/dc14-2073 | 40,715,515 | OBJECTIVE It remains unclear how many hours of sleep are associated with the lowest risk of type 2 diabetes. This meta-analysis was performed to assess the dose-response relationship between sleep duration and risk of type 2 diabetes. RESEARCH DESIGN AND METHODS PubMed and Embase were searched up to 20 March 2014 for p... | 10.1038/s41574-018-0122-1 | Meta-analysis demonstrating an association between sleep duration and the incidence of type 2 diabetes mellitus. |
10.2337/dc15-0302 | 41,210,635 | OBJECTIVE To examine whether a mismatch between chronotype (i.e., preferred sleep timing) and work schedule is associated with type 2 diabetes risk. RESEARCH DESIGN AND METHODS In the Nurses’ Health Study 2, we followed 64,615 women from 2005 to 2011. Newly developed type 2 diabetes was the outcome measure (n = 1,452).... | 10.1038/s41574-018-0122-1 | Study demonstrating the association between social jet lag and the risk of type 2 diabetes mellitus. |
10.1161/cir.0000000000000476 | 103,062,077 | Eating patterns are increasingly varied. Typical breakfast, lunch, and dinner meals are difficult to distinguish because skipping meals and snacking have become more prevalent. Such eating styles can have various effects on cardiometabolic health markers, namely obesity, lipid profile, insulin resistance, and blood pre... | 10.1038/s41574-018-0122-1 | Statement from the American Heart Association on the effects of meal timing and frequency for metabolic health |
10.1126/scitranslmed.aab4176 | 103,830,453 | GM-CSF–producing B cells contribute to multiple sclerosis pathogenesis and the therapeutic action of B cell depletion. | 10.1038/s41582-021-00498-5 | An important study that demonstrated the existence of a functionally specialized B cell subset that exhibits an inflammatory role mediated via effects on monocyte and macrophage activation |
10.1038/s41467-019-14118-w | 83,492,082 | Abstract Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF leukocytes remains superficial. Here, using single cell transcriptomics, we identify a specific location-associated composition and transcriptome of CSF leukocy... | 10.1038/s41582-021-00498-5 | A study that exploited the latest technological advances in single-cell transcriptomics to simultaneously examine blood and CSF cell composition in patients with MS, which revealed compartmentalized T cell and B cell interactions that experiments in an animal model confirmed as functionally relevant in CNS inflammation |
10.1177/1352458512438454 | 2,652,892 | Background: Haematopoietic stem cell transplantation (HSCT) has been tried in the last 15 years as a therapeutic option in patients with poor-prognosis autoimmune disease who do not respond to conventional treatments. Worldwide, more than 600 patients with multiple sclerosis (MS) have been treated with HSCT, most of th... | 10.1038/s41582-021-00498-5 | This study provided the key concept and high-level protocol for randomized controlled trials of AHSCT compared with best standard therapy, a design that has been adopted by subsequent trials, including BEAT-MS and STAR-MS |
10.1126/science.1260825 | 41,670,271 | Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisi... | 10.1038/s41467-018-05467-z | This work suggests that the intrinsic risk factor due to random errors in DNA replication that is common for all humans (i.e. the ‘bad luck’) alone would accunt for over 60% of cancer risk |
10.1126/science.aaf9011 | 41,609,411 | A substantial fraction of mutations in human cancer are attributable to random errors occurring during DNA replication. | 10.1038/s41467-018-05467-z | This work suggests that the intrinsic risk factor due to random errors in DNA replication that is common for all humans (i.e. the ‘bad luck’) alone would accunt for over 60% of cancer driver gene mutations |
10.1073/pnas.1616556114 | 122,467,864 | Recently, it was suggested that tissue variation in cancer risk originates from differences in the number of stem-cell divisions underlying each tissue, leading to different mutation loads. We show that this variation is also correlated with the degree of aberrant CpG island DNA methylation in normal cells. Methylation... | 10.1038/s41467-018-05467-z | Demonstrating a stronger correlation between tissue levels of DNA methylation and cancer burden, these authors argued that epigenetic changes, which can be influenced by exogenous and endogenous factors, could account for even more cancer risk than those argued for due to pure ‘bad luck’ |
10.1126/science.aal2380 | 83,511,848 | Cancer epigenetics in the driver's seat Recent cancer genome projects unexpectedly highlighted the role of epigenetic alterations in cancer development. About half of human cancers were found to harbor mutations in chromatin proteins. In a Review, Flavahan et al. propose that chromatin and epigenetic aberrations have t... | 10.1038/s41467-018-05467-z | While the above work [30] serves mainly as a counter example to the ‘bad luck’ theory , this seminal work demonstrates that genetic, environmental, or metabolic insults can induce overly restrictive or permissive epigenetic landscapes that subsequently contribute to pathogenesis of cancer and other diseases – thus deli... |
10.1002/adma.201606202 | 83,036,817 | The search for highly efficient and low‐cost catalysts is one of the main driving forces in catalytic chemistry. Current strategies for the catalyst design focus on increasing the number and activity of local catalytic sites, such as the edge sites of molybdenum disulfides in the hydrogen evolution reaction (HER). Here... | 10.1038/s41586-021-04105-x | This paper represents the first application of a Weyl semimetal for catalysis |
10.1038/s41467-021-26241-8 | 128,697,399 | Abstract For over 100 years, the group-theoretic characterization of crystalline solids has provided the foundational language for diverse problems in physics and chemistry. However, the group theory of crystals with commensurate magnetic order has remained incomplete for the past 70 years, due to the complicated symme... | 10.1038/s41586-021-04105-x | This paper develops the full theory of topological insulators and metals in magnetic groups |
10.1126/science.aav2334 | 83,035,127 | Bulk–surface correspondence in Weyl semimetals ensures the formation of topological “Fermi arc” surface bands whose existence is guaranteed by bulk Weyl nodes. By investigating three distinct surface terminations of the ferromagnetic semimetal Co 3 Sn 2 S 2 , we verify spectroscopically its classification as a time-rev... | 10.1038/s41586-021-04105-x | This paper shows the relevance of the distinct surface potentials imposed by three different terminations on the modification of the Fermi-arc contour and Weyl node connectivity |
10.1038/s41524-020-0342-5 | 29,083,135 | Abstract The interplay of magnetism and topology opens up the possibility for exotic linear response effects, such as the anomalous Hall effect and the anomalous Nernst effect, which can be strongly enhanced by designing a large Berry curvature in the electronic structure. Magnetic Heusler compounds are a promising cla... | 10.1038/s41586-021-04105-x | This paper systematically investigates the Berry curvature of all magnetic Heusler compounds |
10.1126/science.aav2327 | 20,409,901 | Topological matter is known to exhibit unconventional surface states and anomalous transport owing to unusual bulk electronic topology. In this study, we use photoemission spectroscopy and quantum transport to elucidate the topology of the room temperature magnet Co 2 MnGa. We observe sharp bulk Weyl fermion line dispe... | 10.1038/s41586-021-04105-x | This is the first proof of a ferromagnetic nodal line half metal with surface states that take the form of drumheads via ARPES in Co 2 MnGa |
10.1111/jgh.13731 | 60,758,476 | Abstract Background and Aim Impaired gut‐liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine... | 10.1038/s41575-018-0011-z | This paper describes an example of microbiome-based therapeutics for liver disease management. |
10.1136/gutjnl-2016-313170 | 41,685,438 | Objective Cirrhotics have a high rate of infections, which are increasingly fungal or culture-negative in nature. While infected cirrhotics have bacterial dysbiosis, the role of fungi is unclear. We aimed to evaluate gut bacterial and fungal dysbiosis in cross-sectional and longitudinal analyses of outpatient and inpat... | 10.1038/s41575-018-0011-z | This article discusses the role of the mycobiome in cirrhosis. |
10.1002/hep.29640 | 18,173,827 | Hepatitis B surface antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy. Limited data suggest that stopping Nuc therapy may increase HBsAg loss rate in hepatitis B e antigen–negative patients. A large study was conducted to investigate this issue in more detail. Of the 1,075 hepatitis B e a... | 10.1038/s41575-019-0197-8 | The largest study in HBeAg-negative patients showing much higher HBV surface antigen loss rate after cessation of nucleoside or nucleotide therapy in patients with sustained remission and un-retreated clinical relapse |
10.1002/aenm.201701003 | 83,483,430 | Abstract Li deposition is observed and measured on a solid electrolyte in the vicinity of a metallic current collector. Four types of ion‐conducting, inorganic solid electrolytes are tested: Amorphous 70/30 mol% Li 2 S‐P 2 S 5 , polycrystalline β‐Li 3 PS 4 , and polycrystalline and single‐crystalline Li 6 La 3 ZrTaO 12... | 10.1038/s41560-023-01210-1 | A paper that asserts that lithium intrusion growth is driven by mechanical fractures. |
10.1002/aenm.202000945 | 125,288,470 | Abstract The charge transfer kinetics between a lithium metal electrode and an inorganic solid electrolyte is of key interest to assess the rate capability of future lithium metal solid state batteries. In an in situ microelectrode study run in a scanning electron microscope, it is demonstrated that—contrary to the pre... | 10.1038/s41560-023-01210-1 | An article examining lithium plating on pristine LLZO surfaces using a microprobe technique inside a SEM. |
10.7554/elife.12215 | 103,466,302 | Interpreting visual scenes typically requires us to accumulate information from multiple locations in a scene. Using a novel gaze-contingent paradigm in a visual categorization task, we show that participants' scan paths follow an active sensing strategy that incorporates information already acquired about the scene an... | 10.1038/s41583-018-0078-0 | This paper provides evidence for information-based eye movement strategies using behavioural analysis and Bayesian modelling in humans |
10.1073/pnas.1613844114 | 80,377,840 | In natural behavior, animals have access to multiple sources of information, but only a few of these sources are relevant for learning and actions. Beyond choosing an appropriate action, making good decisions entails the ability to choose the relevant information, but fundamental questions remain about the brain’s info... | 10.1038/s41583-018-0078-0 | This paper demonstrates that oculomotor neurons encode expected information gains in monkeys |
10.7554/elife.13747 | 17,289,842 | When people anticipate uncertain future outcomes, they often prefer to know their fate in advance. Inspired by an idea in behavioral economics that the anticipation of rewards is itself attractive, we hypothesized that this preference of advance information arises because reward prediction errors carried by such inform... | 10.1038/s41583-018-0078-0 | This paper presents a reinforcement learning model of non-instrumental information demand, proposing that, in addition to producing learning, dopaminergic reward prediction errors confer value to predictor states |
10.1523/jneurosci.1128-17.2017 | 39,970,327 | Objects associated with reward draw attention and evoke enhanced activity in visual cortex. What is the underlying mechanism? One possibility is that reward's impact on vision is mediated by unique circuitry that modulates sensory processing, selectively increasing the salience of reward-associated stimuli. Alternative... | 10.1038/s41583-018-0078-0 | This is among the first empirical demonstrations of reward-based and uncertainty-based modulations of visual representations in the human high-level cortex |
10.1523/jneurosci.2816-17.2018 | 45,391,263 | Curiosity is a basic biological drive, but little is known about its behavioral and neural mechanisms. We can be curious about several types of information. On the one hand, curiosity is a function of the expected value of information, serving primarily to help us maximize reward. On the other hand, curiosity can be a ... | 10.1038/s41583-018-0078-0 | This is a demonstration of non-instrumental information value and its neural correlates in humans |
10.1111/bjd.16101 | 45,478,519 | Summary Background Epidemiology data regarding hidradenitis suppurativa (HS) are conflicting and prevalence estimates vary 80-fold, from 0·05% in a population-based study to 4%. Objectives To assess the hypothesis that previous population-based studies underestimated true HS prevalence by missing undiagnosed cases. Met... | 10.1038/s41572-020-0149-1 | This paper is a well-conducted registry study providing a realistic estimate of HS prevalence |
10.4049/jimmunol.0903907 | 124,796,422 | Abstract Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not o... | 10.1038/s41572-020-0149-1 | This paper is the first investigation of the role of cytokines related to activated lymphocytes (for example, IL-17, IL-22, IL-26 and IFN γ and myeloid cells (for example, IL-1β and IL-10), the elements of their pathways and their consequences in the skin of patients with HS |
10.1126/science.1196284 | 60,069,347 | Mutations causing a rare skin disease reveal a signaling pathway that is a drug target for Alzheimer’s disease. | 10.1038/s41572-020-0149-1 | This paper is the first study to demonstrate loss of function mutations in genes encoding γ-secretase, cumulatively found among members of Chinese families with severe HS |
10.1126/science.1260088 | 20,691,552 | Overcoming the limits of the microscope The resolution of a light microscope is limited. Physicists have long since worked out what these limits are and which parameters determine the spatial resolution. Many groups have nevertheless made numerous attempts to overcome these resolution limits. Rather than improving the ... | 10.1038/s41570-020-0170-7 | This work shows the application of free-radical copolymerization of monovinyl/divinyl monomers for biological imaging |
10.1126/science.aag0184 | 62,352,636 | Elasticity, one of the most important properties of a soft material, is difficult to quantify in polymer networks because of the presence of topological molecular defects in these materials. Furthermore, the impact of these defects on bulk elasticity is unknown. We used rheology, disassembly spectrometry, and simulatio... | 10.1038/s41570-020-0170-7 | This work proposes a technique, called symmetric isotopic labelling disassembly spectrometry (SILDaS), to quantify the intrachain links (loops) in polymer networks |
10.1093/bioinformatics/btr137 | 38,740,678 | Abstract Summary: Glycosylation is one of the most important post-translational modifications of proteins, known to be involved in pathogen recognition, innate immune response and protection of epithelial membranes. However, when compared to the tools and databases available for the processing of high-throughput proteo... | 10.1038/s41467-019-11131-x | Proposal of the UniCarb-DB database, the predecessor of the data repository UniCarb-DR proposed in this article |
10.1101/186270 | 71,616,367 | Abstract Detailed descriptions of the development of the hippocampus promise to shed light on the neural foundation of development of memory and other cognitive functions, as well as the emergence of major mental disorders. Hippocampus is a heterogeneous structure with a well characterized internal complexity, but deve... | 10.1038/s41593-018-0078-4 | This paper assessed the structural development of subregions within the hippocampus. Data were from a large accelerated longitudinal study ( n = 270, 678 scans) of 8- to 28-year-olds. The study found heterogeneity of trajectories across region, with some showing early volume increases and others showing nonlinear decre... |
10.1017/s0954579417000438 | 111,678,594 | Abstract Although behavioral and experimental studies have shown links between victimization and antisocial behavior, the neural correlates explaining this link are relatively unknown. In the current study, we recruited adolescent girls from a longitudinal study that tracked youths’ reports of peer victimization experi... | 10.1038/s41593-018-0078-4 | This fMRI study compared adolescents with a history of chronic peer victimization to those with no history of being victimized. The participants with a history of victimization took more risks in a risk-taking task and also showed heightened activation in a number of regions during the task, showing how individual diff... |
10.1097/ipc.0000000000000476 | 58,824,995 | Abstract Hospital-acquired pneumonia and ventilator-associated pneumonia are among the most serious hospital-associated infections. The Infectious Diseases Society of America and the American Thoracic Society have published an update of guidelines for these infections. This updated guideline provides new recommendation... | 10.1038/s41572-021-00259-0 | These guidelines provide risk factors for suspected MDR or XDR microorganisms and recommendations for empirical treatments, use of biomarkers and duration of antibiotic administration |
10.1183/13993003.01144-2016 | 45,561,078 | Pneumonia remains a worldwide health problem with a high rate of morbidity and mortality. Identification of microbial pathogens which cause pneumonia is an important area for optimum clinical management of pneumonia patients and is a big challenge for conventional microbiological methods. The development and implementa... | 10.1038/s41572-021-00259-0 | In-depth revision of available molecular diagnostic techniques for bacterial and viral pneumonia |
10.1242/dev.174177 | 41,240,139 | Dedicated stem cells ensure post-natal growth, repair, and homeostasis of skeletal muscle. Following injury, muscle stem cells (MuSCs) exit from quiescence and divide to reconstitute the stem cell pool and give rise to muscle progenitors. The transcriptomes of pooled MuSCs have provided a rich source of information for... | 10.1038/s41467-020-20760-6 | This is the first largescale scRNA-seq analysis on MuSCs. Using up to 3081 freshly-isolated cells the study confirmed the large transcriptional heterogeneity of the MuSC pool both in homeostatic conditions and in the regenerative environment |
10.1182/blood-2015-05-647172 | 41,774,667 | Key Points Germ-line CEBPA mutations are highly penetrant, causing early-onset de novo AML associated with favorable survival outcomes. Familial CEBPA-mutated AML displays a unique model of disease progression, with recurrence caused by novel, independent leukemic episodes. | 10.1038/s41568-020-00315-z | This work studies diagnosis and relapse leukaemia samples from patients with germline CEBPA mutations and demonstrates that disease recurrence is commonly driven by new, independent clones rather than re-emergence of an existing clone present at diagnosis |
10.1182/blood-2015-09-669937 | 29,309,859 | Key Points Germline GATA2 mutations account for 15% of advanced and 7% of all primary pediatric MDS and do not influence overall survival. The majority (72%) of adolescents with MDS and monosomy 7 carry an underlying GATA2 deficiency. | 10.1038/s41568-020-00315-z | This definitive and comprehensive study demonstrates the prevalence of germline GATA2 mutations in paediatric MDS |
10.1038/s41467-017-01590-5 | 17,686,554 | Abstract Myelodysplastic syndromes (MDS) are uncommon in children and have a poor prognosis. In contrast to adult MDS, little is known about the genomic landscape of pediatric MDS. Here, we describe the somatic and germline changes of pediatric MDS using whole exome sequencing, targeted amplicon sequencing, and/or RNA-... | 10.1038/s41568-020-00315-z | This study is the first to comprehensively profile the genomic landscape of paediatric MDS and describes germline mutations in SAMD9 or SAMD9L in nearly 20% of cases |
10.1530/eje-16-1065 | 49,560,216 | Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic–pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditio... | 10.1038/s41574-020-00437-2 | This review discusses less common causes of hypopituitarism, including infiltrative and infective diseases |
10.1210/endrev/bnz012 | 59,948,974 | Abstract There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic pote... | 10.1038/s41574-020-00437-2 | This review summarizes the effects of oxytocin on metabolism, underlining the growing evidence on the actions in modulating reward-driven food intake |
10.1093/jnen/nlz044 | 100,051,968 | Abstract The cause of sellar region masses in large retrospective series is overwhelmingly pituitary adenomas (84.6%), followed by craniopharyngiomas (3.2%), cystic nonneoplastic lesions (2.8%), inflammatory lesions (1.1%), meningiomas (0.94%), metastases (0.6%), and chordomas (0.5%) (1). While other rare lesions were ... | 10.1038/s41574-020-00437-2 | This review updates the available literature on emerging causes of hypopituitarism, highlighting the importance of the differential diagnosis of sellar and parasellar masses |
10.1530/eje-14-0244 | 123,750,671 | Objective Sheehan's syndrome (SS) is a well-known cause of hypopituitarism resulting from postpartum pituitary necrosis. Because of its rarity in Western society, its diagnosis is often overlooked. We aimed to investigate the clinical, laboratory, and radiological aspects of SS in a large number of patients. Study desi... | 10.1038/s41574-020-00437-2 | This study investigates the clinical, laboratory and radiological aspects of Sheehan syndrome, a common cause of hypopituitarism in developing countries, which is often underdiagnosed because of non-specific symptoms and under-resourced health-care systems |
10.1210/endrev/bnz003 | 121,519,387 | Abstract Some endocrine disorders, including hypophysitis and isolated adrenocorticotropic hormone (ACTH) deficiency, are caused by an autoimmune response to endocrine organs. Although the pathogenesis of some autoimmune endocrine diseases has been elucidated, it remains obscure for most. Anti-PIT-1 hypophysitis (anti-... | 10.1038/s41574-020-00437-2 | This review describes the different mechanisms of pituitary autoimmunity associated with autoimmune hypophysitis, IgG4-related hypophysitis and immune checkpoint-induced hypophysitis, providing a complete and updated revision on this topic |
10.1093/rfs/hhz072 | 123,172,709 | Abstract We propose and implement a procedure to dynamically hedge climate change risk. We extract innovations from climate news series that we construct through textual analysis of newspapers. We then use a mimicking portfolio approach to build climate change hedge portfolios. We discipline the exercise by using third... | 10.1038/s41560-022-01070-1 | The returns of portfolios of stocks sorted on environmental scores co-move with a measure of climate news, indicating that stock prices move in response to climate risk. |
10.1093/rfs/hhab032 | 41,594,024 | Abstract We show that housing markets provide information about the appropriate discount rates for valuing investments in climate change abatement. Real estate is exposed to both consumption and climate risk and its term structure of discount rates is downward sloping, reaching 2.6% for payoffs beyond 100 years. We use... | 10.1038/s41560-022-01070-1 | The prices of houses exposed to sea-level rise risk drop in value (relative to houses not exposed) when real estate participants pay more attention to climate risks, indicating that real estate prices reflect those risks. |
10.1257/aer.20161218 | 18,025,142 | We study potential equilibria in California’s cap-and-trade market for greenhouse gases (GHGs) based on information available before the market started. We find large ex ante uncertainty in business-as-usual emissions and in the abatement that might result from non-market policies, much larger than the reduction that c... | 10.1038/s41560-022-01070-1 | Large uncertainty in business-as-usual emissions implies that the market price in an emissions-trading system is very likely to be determined by an administrative price floor or ceiling |
10.1111/j.1540-6261.1997.tb03809.x | 41,768,193 | ABSTRACT Using data from the 1986 oil price decrease, I examine the capital expenditures of nonoil subsidiaries of oil companies. I test the joint hypothesis that 1) a decrease in cash/collateral decreases investment, holding fixed the profitability of investment, and 2) the finance costs of different parts of the same... | 10.1038/s41560-022-01070-1 | During the 1986 oil price decrease, oil companies significantly reduced their non-oil investment, providing evidence that a decrease in cash/collateral decreases investment, holding fixed the profitability of investment, and that the finance costs of different parts of the same corporation are interdependent |
10.1257/pol.1.2.72 | 100,678,072 | Environmental regulation of industrial pollution is often incomplete; regulations apply to only a subset of facilities contributing to a pollution problem. Policymakers are increasingly concerned about the emissions leakage that may occur if unregulated production can be easily substituted for regulated production. Thi... | 10.1038/s41560-022-01070-1 | The incomplete, market-based regulation of carbon dioxide emissions in California’s electricity sector that exempted out-of-state producers achieved approximately one-third of the total emissions reductions that could have been achieved under complete regulation at more than twice the cost per ton |
10.1126/science.aan4834 | 41,513,283 | Seasonal diets, seasonal microbiota Among the Hadza of western Tanzania, a few hundred people still live in small groups as hunter-gatherers, reliant solely on the wild environment for food. Smits et al. found that the microbiota of these people reflects the seasonal availability of different types of food (see the Per... | 10.1038/s41579-019-0256-8 | This paper provides an excellent example of how the gut microbiome changes dynamically with seasonal dietary shifts as well as westernization |
10.1128/mbio.01604-18 | 61,156,935 | The microbiome has proven to influence health and disease, but how combinations of external factors affect the microbiome is relatively unknown. Diet can cause changes, but this is usually achieved by altering macronutrient ratios and has not focused on dietary protein source or saturated fat intake levels. In addition... | 10.1038/s41579-019-0256-8 | This study shows how healthy individuals respond to dietary fat and protein consumption in a highly individualized pattern |
10.1128/jb.00342-06 | 103,976,016 | ABSTRACT DNA damage and perturbations in DNA replication can induce global transcriptional responses that can help organisms repair the damage and survive. RecA is known to mediate transcriptional responses to DNA damage in several bacterial species by inactivating the repressor LexA and phage repressors. To gain insig... | 10.1038/s41579-022-00694-0 | This work characterizes the transcriptional response to MMC, and also shows that MMC slows replication fork progression in vivo |
10.1073/pnas.1703066114 | 38,945,613 | DNA glycosylases are important editing enzymes that protect genomic stability by excising chemically modified nucleobases that alter normal DNA metabolism. These enzymes have been known only to initiate base excision repair of small adducts by extrusion from the DNA helix. However, recent reports have described both ve... | 10.1038/s41579-022-00694-0 | This work solves the structure of and provides a model for the mechanism of ICL repair by DNA glycosylase AlkZ on AZB adducts |
10.3390/ijms22020952 | 38,377,370 | Double stranded DNA (dsDNA), the repository of genetic information in bacteria, archaea and eukaryotes, exhibits a surprising instability in the intracellular environment; this fragility is exacerbated by exogenous agents, such as ultraviolet radiation. To protect themselves against the severe consequences of DNA damag... | 10.1038/s41579-022-00694-0 | This work is an excellent and comprehensive review covering the structural biology and biochemical mechanisms underlying bacterial NER |
10.1038/ncomms12568 | 39,292,999 | Abstract Nucleotide excision repair (NER) removes chemically diverse DNA lesions in all domains of life. In Escherichia coli , UvrA and UvrB initiate NER, although the mechanistic details of how this occurs in vivo remain to be established. Here, we use single-molecule fluorescence imaging to provide a comprehensive ch... | 10.1038/s41579-022-00694-0 | This paper examines the single-molecule dynamics of UvrA and UvrB in vivo, and shows that lesion recognition takes place in a two-step process with UvrA acting first followed by recruitment of UvrB |
10.1073/pnas.1507386112 | 19,521,673 | MutS is responsible for initiating the correction of DNA replication errors. To understand how MutS searches for and identifies rare base-pair mismatches, we characterized the dynamic movement of MutS and the replisome in real time using superresolution microscopy and single-molecule tracking in living cells. We report... | 10.1038/s41579-022-00694-0 | This manuscript uses a single-molecule approach showing that MutS is recruited to search nascent DNA for mismatches at the replisome, and also shows that MutS tracks with replication forks in synchronized cells |
10.1111/mmi.14158 | 103,491,357 | Summary All organisms possess DNA repair pathways that are used to maintain the integrity of their genetic material. Although many DNA repair pathways are well understood, new pathways continue to be discovered. Here, we report an antibiotic specific DNA repair pathway in Bacillus subtilis that is composed of a previou... | 10.1038/s41579-022-00694-0 | This paper discovers a MMC repair pathway in B. subtilis mediated by newly characterized helicase MrfA and exonuclease MrfB |
10.1093/nar/gkaa1174 | 119,215,311 | Abstract Mitomycin repair factor A represents a family of DNA helicases that harbor a domain of unknown function (DUF1998) and support repair of mitomycin C-induced DNA damage by presently unknown molecular mechanisms. We determined crystal structures of Bacillus subtilis Mitomycin repair factor A alone and in complex ... | 10.1038/s41579-022-00694-0 | This work solves the crystal structure for B. subtilis MrfA helicase, demonstrating a novel translocation mechanism |
10.1126/science.aaa3245 | 123,204,799 | How the brain sorts and routes messages How do higher brain areas communicate with each other? Do they send out all computations equally to all target areas and leave the recipient to extract the needed and relevant information? Or does the transmitting region package and route computations differentially to distinct t... | 10.1038/s41583-019-0125-5 | Combining antidromic stimulation with recording, this study finds that ventral CA1 cells exhibit pronounced heterogeneity in their feature selectivity, and this heterogeneity correlates with their downstream targets |
10.1126/science.1110449 | 62,214,254 | Hippocampal place cells are a model system of how the brain constructs cognitive representations and of how these representations support complex behavior, learning, and memory. There is, however, a lack of detailed knowledge about the properties of hippocampal afferents. We recorded multiple single units from the hipp... | 10.1038/s41583-019-0125-5 | This study shows that neurons in the medial and lateral entorhinal cortex show prominent and minimal spatial modulation, respectively, demonstrating a dissociation between spatial and non-spatial inputs to the hippocampus |
10.1126/sciadv.aaw9883 | 103,775,030 | Over the past decade, the Arctic has warmed by 0.75°C, far outpacing the global average, while Antarctic temperatures have remained comparatively stable. As Earth approaches 2°C warming, the Arctic and Antarctic may reach 4°C and 2°C mean annual warming, and 7°C and 3°C winter warming, respectively. Expected consequenc... | 10.1038/s41558-019-0688-1 | Reviews how Arctic warming has outpaced the global average, with wide-reaching consequences for tundra ecosystems |
10.1111/j.1365-2486.2009.02047.x | 39,996,960 | Abstract Growth in arctic vegetation is generally expected to increase under a warming climate, particularly among deciduous shrubs. We analyzed annual ring growth for an abundant and nearly circumpolar erect willow ( Salix lanata L.) from the coastal zone of the northwest Russian Arctic (Nenets Autonomous Okrug). The ... | 10.1038/s41558-019-0688-1 | Links spectral greening with both warming and tundra shrub growth in the Russian Arctic |
10.1111/gcb.12647 | 80,849,056 | Abstract Satellite‐derived indices of photosynthetic activity are the primary data source used to study changes in global vegetation productivity over recent decades. Creating coherent, long‐term records of vegetation activity from legacy satellite data sets requires addressing many factors that introduce uncertainties... | 10.1038/s41558-019-0688-1 | Reports conflicting patterns in spectral greening trends from different satellite datasets, highlighting critical uncertainties in the links between satellite-observed spectral greening trends and in-situ vegetation change |
10.1038/s41598-016-0028-x | 104,425,269 | Abstract Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness... | 10.1038/s41467-020-19020-4 | This paper demonstrates simultaneous enhancement iron, zinc, and provitamin A in rice seeds, confirming the potential of genetic engineering to increase multiple micronutrients using a single DNA insertion |
10.1038/s41467-020-14981-y | 20,746,021 | Abstract Targeted insertion of transgenes at pre-determined plant genomic safe harbors provides a desirable alternative to insertions at random sites achieved through conventional methods. Most existing cases of targeted gene insertion in plants have either relied on the presence of a selectable marker gene in the inse... | 10.1038/s41467-020-19020-4 | Here, a cassette containing genes for provitamin A accumulation is successfully introduced in a safe-harbor in the rice genome, which allows creation of provitamin A-rich rice lines without usage of a selectable marker |
10.1002/aepp.13044 | 104,001,217 | Abstract New plant breeding technologies (NPBTs), including genetically modified and gene‐edited crops, offer large potentials for sustainable agricultural development and food security while addressing shortcomings of the Green Revolution. This article reviews potentials, risks, and actually observed impacts of NPBTs.... | 10.1038/s41467-020-19020-4 | This article discusses the current and potential impact of crops obtained via genetic engineering and gene-editing technologies, and covers regulatory issues associated with their implementation |
10.1162/neco.2009.10-08-881 | 107,326,543 | Many image segmentation algorithms first generate an affinity graph and then partition it. We present a machine learning approach to computing an affinity graph using a convolutional network (CN) trained using ground truth provided by human experts. The CN affinity graph can be paired with any standard partitioning alg... | 10.1038/s41592-022-01712-y | This paper shows the first conceptualization of the use of affinity graphs for neuron segmentation in EM volumes. |
10.1038/s42003-018-0261-x | 62,235,855 | Abstract This scientometric review of genome-wide association studies (GWAS) from 2005 to 2018 (3639 studies; 3508 traits) reveals extraordinary increases in sample sizes, rates of discovery and traits studied. A longitudinal examination shows fluctuating ancestral diversity, still predominantly European Ancestry (88% ... | 10.1038/s41588-023-01328-8 | A review article that presents relevant discoveries and evolution of GWAS since 2005. |
10.1111/acel.12651 | 104,016,042 | Summary The dietary intake of ω‐3 polyunsaturated fatty acids has been linked to a reduction in the incidence of aging‐associated disease including cardiovascular disease and stroke. Additionally, long‐lived Caenorhabditis elegans glp‐1 germ line‐less mutant animals show a number of changes in lipid metabolism includin... | 10.1038/s41589-021-00837-z | Direct evidence showing lifespan extension by a PUFA, α-linolenic acid, as well as the discovery of a spontaneously oxidized product from a PUFA that extends lifespan |
10.1126/science.1258857 | 29,084,123 | Lysosomes are crucial cellular organelles for human health that function in digestion and recycling of extracellular and intracellular macromolecules. We describe a signaling role for lysosomes that affects aging. In the worm Caenorhabditis elegans , the lysosomal acid lipase LIPL-4 triggered nuclear translocalization ... | 10.1038/s41589-021-00837-z | The discovery of oleoylethanolamine as a longevity-promoting metabolite and its signaling mechanism through the fatty acid-binding protein LBP-8 and the NHR-80/HNF4–NHR-49/PPARα nuclear receptor complex |
10.1038/s41467-017-02651-5 | 38,399,087 | Abstract The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is... | 10.1038/s41589-021-00837-z | This study revealed that microbiota-derived SFCAs are regulators of epigenetics, a hallmark of host aging |
10.1002/cphc.201800545 | 83,018,709 | Abstract Retinoids play critical roles in development, immunity, and lipid metabolism, and their deficiency leads to various human disorders. Yet, tools for sensing retinoids in vivo are lacking, which limits the understanding of retinoid distribution, dynamics and functions in living organisms. Here, using hyperspectr... | 10.1038/s41589-021-00837-z | A spatiotemporal dynamic study of retinoids with SRS that positively correlated retinoids with fat storage and survival in dauers and with fat unsaturation and lifespan upon feeding with a high-glucose diet in C. elegans |
10.1126/science.1254803 | 102,257,728 | After an infection, pathogen-specific tissue-resident memory T cells (T RM cells) persist in nonlymphoid tissues to provide rapid control upon reinfection, and vaccination strategies that create T RM cell pools at sites of pathogen entry are therefore attractive. However, it is not well understood how T RM cells provid... | 10.1038/s41590-018-0114-2 | The study in ref. 25 reports an essential early role for TRM cells in the activation of the surrounding tissue to establish protection after re-infection |
10.1038/ncomms16073 | 102,293,372 | Abstract The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8 + T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8 + T cells and Trm cells remains po... | 10.1038/s41590-018-0114-2 | The study in ref. 49 formally establishes an important contribution of tissue resident immunity to tumor control through parabiosis experiments and pharmacological blockade of egress from lymph nodes. It also shows that T CM cells retain the ability to make T RM cells |
10.1084/jem.20061524 | 41,121,183 | Various T cell adhesion molecules and their cognate receptors on target cells promote T cell receptor (TCR)–mediated cell killing. In this report, we demonstrate that the interaction of epithelial cell marker E-cadherin with integrin αE(CD103)β7, often expressed by tumor-infiltrating lymphocytes (TILs), plays a major r... | 10.1038/s41590-018-0114-2 | The study in ref. 99 showed that the hallmark epithelial T RM cell molecule CD103 has a function in killing tumor cells |
10.1126/scitranslmed.3004888 | 101,381,914 | Mucosal vaccination induces targeted CD8 + T cell homing to inhibit mucosal tumors. | 10.1038/s41590-018-0114-2 | This (ref. 101) was an early study showing that a tissue-specific vaccine elicits T RM cells and elicits more-efficient anti-tumor immunity than does a systemic vaccine. |
10.1200/jco.2017.77.1592 | 83,045,056 | Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non–breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We ... | 10.1038/s41585-019-0243-x | An important study that highlighted the fact that despite the earlier regulatory approval of breakthrough-therapy-designated drugs, no evidence exists that these drugs provide improvements in safety or novelty |
10.1002/cncr.23452 | 100,446,208 | Abstract BACKGROUND. Observational data are used increasingly to assess the effectiveness of therapies. However, selection biases are likely to have an impact on results and threaten the validity of these studies. METHODS. The primary objective of the current study was to explore the effect of selection biases in obser... | 10.1038/s41585-019-0243-x | This paper highlights the limitations of observational data, particularly those derived from claims registries such as SEER |
10.1002/cncr.22436 | 18,171,866 | Abstract BACKGROUND. Providers play a vital role in the successful recruitment of underrepresented patients to cancer clinical trials because they often introduce the opportunity of clinical trials. The purpose of the current systematic review was to describe provider‐related factors influencing recruitment of underrep... | 10.1038/s41585-019-0243-x | A systematic review that highlights the role that providers and caregivers have in adversely influencing the recruitment of under-represented groups to clinical trials |
10.1126/science.aaj2239 | 103,762,457 | Positives and negatives of methylated CpG When the DNA bases cytosine and guanine are next to each other, a methyl group is generally added to the pyrimidine, generating a mCpG dinucleotide. This modification alters DNA structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. s... | 10.1038/s41576-022-00512-6 | This work using high-throughput SELEX demonstrates widespread methylation-sensitive binding of mammalian TFs |
10.1126/science.abb0074 | 19,191,956 | Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution... | 10.1038/s41576-022-00512-6 | This work using high-throughput binding assays and structural determination demonstrates that OCT4–SOX2 can engage partial motifs at the entry–exit sites of a nucleosome |
10.1038/s41467-020-17959-y | 124,123,874 | Abstract During cellular reprogramming, the pioneer transcription factor GATA3 binds chromatin, and in a context-dependent manner directs local chromatin remodeling and enhancer formation. Here, we use high-resolution nucleosome mapping in human cells to explore the impact of the position of GATA motifs on the surface ... | 10.1038/s41576-022-00512-6 | This work on the structure of GATA3 on the nucleosome demonstrates tandem motif engagement at high resolution |
10.1101/gad.176826.111 | 62,622,635 | Transcription factors are adaptor molecules that detect regulatory sequences in the DNA and target the assembly of protein complexes that control gene expression. Yet much of the DNA in the eukaryotic cell is in nucleosomes and thereby occluded by histones, and can be further occluded by higher-order chromatin structur... | 10.1038/s41576-022-00512-6 | This work presents a model of pioneer factor activity in the genome, whereby specialized TFs are the first in a hierarchy of factors that enable the activation of regulatory regions |
10.1038/s41467-019-13960-2 | 42,557,537 | Abstract Establishing gene regulatory networks during differentiation or reprogramming requires master or pioneer transcription factors (TFs) such as PU.1, a prototype master TF of hematopoietic lineage differentiation. To systematically determine molecular features that control its activity, here we analyze DNA-bindin... | 10.1038/s41576-022-00512-6 | This study reveals that the PU.1 TF utilizes BRG1 to enable genomic binding and opening of chromatin in vivo |
10.1126/science.aaz1646 | 83,123,939 | Gene regulation is chiefly determined at the level of individual linear chromatin molecules, yet our current understanding of cis-regulatory architectures derives from fragmented sampling of large numbers of disparate molecules. We developed an approach for precisely stenciling the structure of individual chromatin fib... | 10.1038/s41576-022-00512-6 | This work shows that FiberSeq generates single-molecule data on TFs and nucleosomes that span kilobases using a footprinting and long-read sequencing technique |
10.1126/scitranslmed.aau3259 | 17,665,857 | Cancer immunotherapy with immune checkpoint inhibitors (CPIs) and interleukin-2 (IL-2) has demonstrated clinical efficacy but is frequently accompanied with severe adverse events caused by excessive and systemic immune system activation. Here, we addressed this need by targeting both the CPI antibodies anti–cytotoxic T... | 10.1038/s41568-019-0186-9 | This study illustrates that conjugation or fusion of a collagen-binding domain to biologics promotes their accumulation in tumours, improving the therapeutic index of systemically administered immunotherapy |
10.1126/scitranslmed.aar1916 | 107,290,410 | Prolonged perioperative delivery of immunotherapy prevents local tumor recurrence and eliminates established spontaneous metastases. | 10.1038/s41568-019-0186-9 | This study shows that reprogramming the post-resection milieu from immunosuppressive to immunostimulatory not only prevents local recurrence but also eradicates disseminated disease, and that sustaining drug exposure locally is required in order to achieve a durable survival benefit |
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