Search

The conventional way of classifying metastatic cancers according to their organ of origin is denying people access to drugs that could help them.

Artificial-intelligence models are typically used online, but a host of openly available tools is changing that. Here’s how to get started with local AIs.

The field is taking a leap forward thanks to innovative technologies, such as artificial intelligence. Researchers must improve consent procedures and public involvement.

Letter to the Editor

A self-driving lab system spent half a year engineering enzymes to work at higher temperatures.

Wiping out one part of the brain can break the thrall of smoking.

A new security approach would let users input patterns instead of words to verify identity

Drug affects previously overlooked brain cells that have a crucial role in memory formation.

A metal–polymer composite conducts electricity and conforms to the skin, making it suitable for medical devices applied directly to the body.

Information from satellites, mobile phones and other sources is not a panacea for international-development problems, warns Joshua Blumenstock. Information from satellites, mobile phones and other sources is not a panacea for international-development problems, warns Joshua Blumenstock.

Cuttlefish, an octopus relative, retain their cognitive powers as they grow older.

The Arabian Peninsula is dotted with hundreds of mysterious structures dating to the sixth millennium BC.

Glutathione plays many parts in living organisms, and new methods for the oxidation of this tripeptide reveal some of them. This review of the present situation ends with some suggestions for the future.

Microorganisms in the gut influence fear-related learning. The results of a study that reveals some of the mechanistic underpinnings of this phenomenon promise to boost our understanding of gut–brain communication.

Even before their eyes open and their fur grows out, young mice can distinguish a mother figure from a stranger.

Multiple cavities pit the teeth excavated from a Viking settlement found in modern-day Sweden.

Rather than building objects layer by layer, the printer creates whole structures by projecting light into a resin that solidifies.

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children1,2, and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma3. Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH).ELP1was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent–offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHHα subtype4and characterized by universal biallelic inactivation of ELP1owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34) position5,6. Tumours from patients with ELP1-associated MBSHHwere characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems7–9. Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.

In cancer, recurrent somatic single-nucleotide variants—which are rare in most paediatric cancers—are confined largely to protein-coding genes1–3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5′ splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5′ cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

Effective ocean management and the conservation of highly migratory species depend on resolving the overlap between animal movements and distributions, and fishing effort. However, this information is lacking at a global scale. Here we show, using a big-data approach that combines satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space-use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively), and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of fishing effort in marine areas beyond national jurisdictions (the high seas). Our results demonstrate an urgent need for conservation and management measures at high-seas hotspots of shark space use, and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real-time, dynamic management.

Global dust storms on Mars are rare1,2but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars4. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes5,6, as well as a decrease in the water column at low latitudes7,8. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H2O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals3. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.

The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today1. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations2–5. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere6,7, which—given methane’s lifetime of several centuries—predicts an even, well mixed distribution of methane1,6,8. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections2,4. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater4would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally.

Simulations of the levels of nitrogen, methane and carbon monoxide over thousands of years confirm the existence of a nitrogen glacier in Sputnik Planitia, Pluto’s deepest basin.

The Tharsis region is the largest volcanic complex on Mars and in the Solar System. Young lava flows cover its surface (from the Amazonian period, less than 3 billion years ago) but its growth started during the Noachian era (more than 3.7 billion years ago). Its position has induced a reorientation of the planet with respect to its spin axis (true polar wander, TPW), which is responsible for the present equatorial position of the volcanic province. It has been suggested that the Tharsis load on the lithosphere influenced the orientation of the Noachian/Early Hesperian (more than 3.5 billion years ago) valley networks and therefore that most of the topography of Tharsis was completed before fluvial incision. Here we calculate the rotational figure of Mars (that is, its equilibrium shape) and its surface topography before Tharsis formed, when the spin axis of the planet was controlled by the difference in elevation between the northern and southern hemispheres (hemispheric dichotomy). We show that the observed directions of valley networks are also consistent with topographic gradients in this configuration and thus do not require the presence of the Tharsis load. Furthermore, the distribution of the valleys along a small circle tilted with respect to the equator is found to correspond to a southern-hemisphere latitudinal band in the pre-TPW geographical frame. Preferential accumulation of ice or water in a south tropical band is predicted by climate model simulations of early Mars applied to the pre-TPW topography. A late growth of Tharsis, contemporaneous with valley incision, has several implications for the early geological history of Mars, including the existence of glacial environments near the locations of the pre-TPW poles of rotation, and a possible link between volcanic outgassing from Tharsis and the stability of liquid water at the surface of Mars.

With the explosion of digital media and technologies, scholars, educators and the public have become increasingly vocal about the role that an ‘attention economy’ has in our lives1. The rise of the current digital culture coincides with longstanding scientific questions about why humans sometimes remember and sometimes forget, and why some individuals remember better than others2–6. Here we examine whether spontaneous attention lapses—in the moment7–12, across individuals13–15and as a function of everyday media multitasking16–19—negatively correlate with remembering. Electroencephalography and pupillometry measures of attention20,21were recorded as eighty young adults (mean age, 21.7 years) performed a goal-directed episodic encoding and retrieval task22. Trait-level sustained attention was further quantified using task-based23and questionnaire measures24,25. Using trial-to-trial retrieval data, we show that tonic lapses in attention in the moment before remembering, assayed by posterior alpha power and pupil diameter, were correlated with reductions in neural signals of goal coding and memory, along with behavioural forgetting. Independent measures of trait-level attention lapsing mediated the relationship between neural assays of lapsing and memory performance, and between media multitasking and memory. Attention lapses partially account for why we remember or forget in the moment, and why some individuals remember better than others. Heavier media multitasking is associated with a propensity to have attention lapses and forget.

Natural resistance of mice to infections with Salmonella typhimurium and Leishmania donovani is regulated by chromosome 1 gene(s) designated Ity and Lsh, respectively1,2. Given the fact that these two microorganisms are taxonomically and antigenically distinct, and yet the host response to them is regulated by the same locus or complex3,4, one might expect that the resistance to other intracellular pathogens would be controlled similarly. Innate resistance of inbred mice to infection with Mycobacterium bovis (BCG) is regulated by a single, dominant, autosomal gene designated Bcg which is known to exist in two allelic forms: resistant Bcgrand susceptible Bcgs(ref. 5). The distribution of Bcgrand Bcgsalleles, among a total of 14 inbred and 38 recombinant inbred (BXD and BXH) strains, matches exactly that established for resistant and susceptible alleles of Lsh (gene controlling resistance to Leishmania donovani) and Ity (gene controlling resistance to Salmonella typhimurium), suggesting that resistance to all these pathogens is controlled by the same chromosome 1 locus. The existence of such a chromosomal locus is further supported by the Bcg–Lsh and Bcg–Ity linkage as established by formal backcross analysis.

Simple oligonucleotide maps can be obtained by two-dimensional paper electrophoresis from enzyme digests of 5SRNA from KBcarcinoma ribosomes. These maps can be distinguished from those obtained from 5SRNA derived from E. coliand from RNA components of low molecular weight derived from KBcells with and without adenovirus infection.

The model organism Caenorhabditis elegansis quick to forget a notable odour — unless it is chilled or given lithium.

THE β-thalassaemias are a heterogeneous group of hereditary haematological disorders in which there is absent or decreased synthesis of the β globin chain of normal human adult haemoglobin, HbA (α2β2)1. When β chain synthesis is totally absent, the condition can be referred to as β°-thalassaemia, in contrast to β+-thalassaemia in which some β chain synthesis occurs. The genetics and manifestations of β°-thalassaemia are rather varied. In the heterozygote, there may be either increased levels of the minor haemoglobin, HbA2(α2δ2) (‘A2-thalassaemia’), or normal levels of HbA2with elevated levels of foetal haemoglobin, HbF (α2γ2), (‘δβ-thalassaemia’ or ‘F-thalassaemia’). Homozygous β°-thalassaemia of the A2variety is clinically severe, and has been described mainly in the Ferrara region of northen Italy and in Thailand, although it is found sporadically in other racial groups; the red cells of these individuals contain mainly HbF with variable amounts of HbA2, but no HbA. Homozygous δβ-thalassaemia is extremely rare, having been described in only eight individuals from four different families1; it is associated with only mild symptoms; the red cells of these individuals contain 100% HbF, and there is total absence of both HbA and HbA2.

In hereditary persistence of fetal haemoglobin (HPFH), there is a uniformly high level of synthesis of fetal haemoglobin (Hb F: α2γ2) in all red cells of affected adults. Other hereditary disorders of human haemoglobin synthesis may also be associated with persistent synthesis of Hb F into adult life, but usually at a lower level and in only a selected population of red cells. Previous studies in the common type of HPFH that occurs in blacks have demonstrated the presence of a total deletion of the linked β- and δ-globin genes of the adult haemoglobins Hb A (α2β2) and Hb A2(α2δ2)1–3, including approximately 4 kilo-bases of the DNA flanking the 5′ end of the δ gene. In contrast, δβ-thalassaemia, in which Hb F synthesis is not as elevated or uniform as in HPFH, is associated with a partial deletion of the δ gene that leaves intact the 5′-flanking DNA of the gene1–5. These results provided support for previous theories6that regulatory sequences involved in the suppression of γ-globin gene expression might be located between the γ- and δ-globin genes, and that deletion of these sequences might be responsible for the continued expression of γ-globin genes in HPFH. To extend these observations, gene mapping studies of the non-α-globin genes have now been carried out in two additional individuals wth HPFH using restriction endonuclease digestion and gel blotting of total cellular DNA according to the method of Southern16. The results indicate that the molecular defects associated with HPFH are heterogeneous even in cases with similar phenotypes such as in the common variety of HPFH that occurs in blacks.

ANAEMIA is a frequent complication of thyroid dysfunction in man, and often remains unexplained, responding only to thyroid hormone replacement therapy1,2. Thyroid hormone has recently been shown to influence the rate of red blood cell and haemoglobin production3–7. In addition to stimulating erythropoietin (Ep) production3, thyroid hormone has been reported to act directly on haematopoietic precursors4,5. The enhancement of murine and canine in vitro erythroid colony growth by thyroid hormone6,7suggests that this hormone may have a direct role in the modulation of erythroid proliferation. Studies of murine erythropoiesis support the existence of two distinct, age-structured, Ep responsive populations of committed erythroid precursor cells: the early committed erythroid burst forming unit (BFU-E) and the late committed erythroid colony forming unit (CFU-E)8. These populations are distinguished by cell volume, responsiveness to Ep, and proliferative capacity. The BFU-E, a cell which arises from the pluripotent stem cell soon after its commitment to the erythroid line and which has a high Ep-responsive proliferative capacity, seems to be the precursor of the CFU-E, a cell of lower proliferative capacity. Thyroid hormone has been shown to enhance in vitro erythroid colony formation by canine marrow cells, an effect that may be mediated by a receptor with β2-adrenergic properties7. Velocity sedimentation analysis revealed that colony-forming cells stimulated by this hormone sedimented more slowly than colony-forming cells responding to Ep alone7. Here, we have extended these studies to human marrow cells and have shown that the ability of thyroid hormone to stimulate the erythroid committed progenitor cell does not seem to be a function of the state of differentiation of this cell. Both CFU-E-derived and BFU-E-derived colony formation were enhanced by the hormone.

Long thought to be a glitch of memory, researchers are coming to realize that the ability to forget is crucial to how the brain works. Long thought to be a glitch of memory, researchers are coming to realize that the ability to forget is crucial to how the brain works.

The surname of author Cathy Quantin-Nataf was misspelled ‘Quantin-Nata’, authors Ehouarn Millour and Roland Young were missing from the ACS and NOMAD Science Teams list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online.

The surname of author Cathy Quantin-Nataf was misspelled ‘Quantin-Nata’ , authors Ehouarn Millour and Roland Young were missing from the ACS Science Team list, and minor changes have been made to the author and affiliation lists; see accompanying Amendment. These errors have been corrected online.

People are able to make themselves forget disturbing images.

Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, α2γ2) in the absence of eryth-ropoietic stress1. Several genetic types have been discerned based on the level of HbF produced, the relative contributions of the duplicated fetal (Gγ and Aγ) globin genes, and the presence or absence of deletions involving the β and δ genes in cis to the mutation2,3. Greek HPFH is a non-deletion variety in which heterozygotes produce 10–20% HbF, predominantly due to overproduction of the Aγ chain4–9. We have cloned a 40-kilobase (kb) region of the β-globin cluster from a Greek HPFH allele and report here that a point mutation (G→A) occurs 117 base pairs (bp) 5′ to the cap site of the Aγ-globin gene, just upstream of the distal CCA AT sequence. The corresponding region of the Gγ-globin gene is normal. We discuss the implications of this finding for the developmental regulation of globin gene expression.

The form of hereditary persistence of fetal haemoglobin (HPFH) that commonly occurs in black populations is an inherited disorder of haemoglobin synthesis characterized by a uniformly high level of fetal haemoglobin (HbF) synthesis in all the erythroid cells of affected adult individuals1,2. The precise molecular basis of the HPFH phenotype remains unknown, but is of great interest because of the knowledge that could be gained, through its understanding, of the mechanisms that regulate the expression of globin genes during development. The most common form of HPFH in black populations is associated with an extensive deletion that includes the normal adult (δ and β) globin genes and adjacent flanking DNA3–8. To investigate this disorder in more detail, we have cloned the DNA encompassing the region of the gene deletion in a case of HPFH and have determined the nucleotide sequence across the 5′ end point of the deletion within the non-α-globin gene complex. We report here that this end point maps at the midpoint of a member of the ‘AluI’ family of repetitive sequences located approximately 4 kilobases (kb) to the 5′ side of the δ-globin gene. Such repetitive sequences may be ‘hot spots’ of recombination, and are possibly involved in regulating gene expression.

State your main finding in your title, and don’t forget to use the word ‘but’, says Bruce Kirchoff.

‘Set and forget’ devices are the most effective forms of birth control available. But few people choose to use them.

THE study of metals possesses an irresistible charm for us, quite apart from its vast national importance. How many of us made our first scientific experiment by watching the melting of lead, little thinking that we should hardly have done a bad life's work if the experiment had been our last, provided we had only understood its full significance. How few of us forget that we wistfully observed at an early age the melting in an ordinary fire of some metallic toy of our childhood; and the experiment has, like the “Flat iron for a farthing,” in Mrs. Ewing's charming story, taken a prominent place in literature which claims to be written for children. Hans Andersen's fairy tale, for instance, the “History of a Tin Soldier,” has been read, by children of all ages and of most nations. The romantic incidents of the soldier's eventful career need not be dwelt upon; but I may remind you that at its end he perished in the flames of an ordinary fire, and all that could subsequently be found of him was a small heart-shaped mass. There is no reason to doubt the perfect accuracy of the story recorded by Andersen, who at least knew the facts, though his statement is made in popular language. No analysis is given of the tin soldier; in a fairy tale it would have been out of place, but the latest stage of his evolution is described, and the record is sufficient to enable us to form the opinion that he was composed of both tin and lead, certain alloys of which metals will burn to ashes like tinder. His uniform was doubtless richly ornamented with gold lace. Some small amount of one of the rarer metals had probably—for on this point the history is silent—found its way into his constitution, and by uniting with the gold, formed the heart-shaped mass which the fire would not melt, as its temperature could not have exceeded 1000°; for we are told that the golden rose, worn by the artistewho shared the soldier's fate, was also found unmelted. The main point is, however, that the presence of one of the rarer metals must have endued the soldier with his singular endurance, and in the end left an incorruptible record of him.

I DO not wish to criticize in the least Prof. Lankester's valuable statement in your last issue, with which I entirely agree; but I desire to point out that unless some energetic action is taken very soon we are likely to be farther than ever from the ideal which he has in view—namely, the establishment of a strong professorial University in London. The only scheme at present in the field is that put forward by the Councils of University and King's Colleges in the proposed charter for an Albert University. This scheme has never met with the cordial support of a large section at least of the teaching staff of University College, and for the very obvious reason that it does not constitute a professorial University, but creates a new examining body on which the two Colleges will be, in the beginning at any rate, largely represented. The Albert University charter would create a second Victoria University in London. Now, both Mr. Dyer and Prof. Lankester are agreed that we do not want a federal University like Victoria in London ; but they seem to forget that this pettifogging excuse for a University—a scheme drafted by bureaucratic rather than academic minds—is the only scheme in the field, and that, further, the Lord President of the Council has determined to hear by counsel, on an early day in June, what can be said for and against this scheme. It is further rumoured that the Burlington House Senate intends, after its recent discomfiture, to remain absolutely neutral. The danger, then, that we shall have a repetition in London of the difficulties of Manchester is a very immediate one. Let me point out exactly the anomalies of the Albert scheme. In the first place, it does not create a teaching University, but a new examining body. The University as such will have no control over the appointment of the professoriate either at University or King's Colleges, it will have no funds to dispose of and there will be nothing to prevent rival second-rate teachers and teaching equipment instead of first-rate central teaching and central laboratories. For example, at the present time, putting aside the Central Institute, we have some half-dozen second-rate physical laboratories in London, but not a really first-class one worthy of a modern University among them. So long as there is competition between the Colleges, so long as they possess a double staff competing at every turn with each other for students' fees, this is unlikely to be remedied. Prof. Lankester speaks of a union of King's and University, and talks about their combined resources. The fusion of these two Colleges would certainly be the first stage to a true professorial University in London, but there is nothing in the Albert charter to bring this about: it unites the two Colleges not for teaching but for examining purposes. But what is still worse, while these two Colleges will remain autonomous, the Albert charter proposes to admit any further autonomous bodies, the teaching of which can be shown to have reached a certain academic standard. These bodies will not be absorbed, but their independent staffs will be represented on the Faculties and Senate. Here we have in fact the University of London over again,—at first composed almost entirely of the two Colleges, afterwards embracing all sorts and conditions of institutions in London, and ultimately open to every isolated text-book reader in the universe. It cannot be therefore too strongly insisted upon that the Albert charter, if granted, will not call into existence a professorial University, but federate a group, and an ever-widening group, of competing institutions for the purposes of examination. If it sheds for a time any additional lustre on the teaching staffs of the two Colleges—which I am much inclined to doubt—it will not achieve, what most of us have at heart, the establishment in London, at any rate in the germ, of a great University in the Scottish or German sense. A University, on the scale we hope for, would absorb the plant of University and King's Colleges, of the Royal College of Science, and of the Central Institute without the least difficulty. With the death or transference of existing teachers, whose pecuniary interests would have of course to be carefully safeguarded, special branches of higher teaching and research might be localized at these various centres,1and we thus might reach in the future an efficient University organization in London. This may indeed be considered a merely ideal future, but any scheme like the proposed Albert University, which will only impede its ultimate realization, ought to meet with strenuous opposition from those who believe that a great professorial University must sooner or later be established in London.

THE notion of “balance” ordinarily implies some underlying insecurity or liability to loss of equilibrium. Thus a pencil set up on its butt end may be technically in stable equilibrium, yet, because the centre of gravity lies some way above the relatively small area of support, we speak of the condition as one of “precarious balance”. The situation of a man standing erect is somewhat similar, though here the posture is maintained by muscular activity which is reflexly adjusted to counter the effects of forces that might disturb the equilibrium. These adjustments are usually so successful, and falling is consequently so unusual, that we tend to forget the inherent insecurity of the posture.