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The RNA world concept 1 is one of the most fundamental pillars of the origin of life theory 2 – 4 . It predicts that life evolved from increasingly complex self-replicating RNA molecules 1 , 2 , 4 . The question of how this RNA world then advanced to the next stage, in which proteins became the catalysts of life and RNA reduced its function predominantly to information storage, is one of the most mysterious chicken-and-egg conundrums in evolution 3 – 5 . Here we show that non-canonical RNA bases, which are found today in transfer and ribosomal RNAs 6 , 7 , and which are considered to be relics of the RNA world 8 – 12 , are able to establish peptide synthesis directly on RNA. The discovered chemistry creates complex peptide-decorated RNA chimeric molecules, which suggests the early existence of an RNA–peptide world 13 from which ribosomal peptide synthesis 14 may have emerged 15 , 16 . The ability to grow peptides on RNA with the help of non-canonical vestige nucleosides offers the possibility of an early co-evolution of covalently connected RNAs and peptides 13 , 17 , 18 , which then could have dissociated at a higher level of sophistication to create the dualistic nucleic acid–protein world that is the hallmark of all life on Earth. Peptide synthesis can take place directly on RNA, which suggests how a nucleic acid–protein world might have originated on early Earth.

Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25–200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose–response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT2A receptor activation.

Rationale 3,4-Methylenedioxymethamphetamine (MDMA) is used recreationally and investigated as an adjunct to psychotherapy. Methylphenidate and modafinil are psychostimulants that are used to treat attention-deficit/hyperactivity disorder and narcolepsy, respectively, but they are also misused as cognitive enhancers. Little is known about differences in the acute effects of equally cardiostimulant doses of these stimulant-type substances compared directly within the same subjects. Methods We investigated the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg), and placebo in a double-blind, cross-over study in 24 healthy participants. Acute drug effects were tested using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI). Results All active drugs produced comparable hemodynamic and adverse effects. MDMA produced greater increases in pupil dilation, subjective good drug effects, drug liking, happiness, trust, well-being, and alterations in consciousness than methylphenidate or modafinil. Only MDMA reduced subjective anxiety and impaired fear recognition and led to misclassifications of emotions as happy on the FERT. On the SADI, only MDMA produced sexual arousal-like effects. Only MDMA produced marked increases in cortisol, prolactin, and oxytocin. In contrast to MDMA, methylphenidate increased subjective anxiety, and methylphenidate and modafinil increased misclassifications of emotions as angry on the FERT. Modafinil had no significant subjective drug effects but significant sympathomimetic and adverse effects. Conclusions MDMA induced subjective, emotional, sexual, and endocrine effects that were clearly distinct from those of methylphenidate and modafinil at the doses used.

This study investigates the lifetime and temporal evolution of physical properties of trade‐wind cumuli based on tracking individual clouds in observations with the Advanced Baseline Imager aboard the geostationary GOES‐16 satellite during the “ElUcidating the RolE of Cloud–Circulation Coupling in ClimAte” (EUREC4A) campaign east of Barbados in winter 2020. A first application of our upgraded cloud‐tracking toolbox to measurements with high spatio‐temporal resolution (2 × 2 km2 and 1 min) provides probability density functions of lifetime and area of clouds that develop as a consequence of meso‐to‐synoptic scale motions. By separately considering clouds that exist during daytime and live in distinct lifetime intervals, we find that shallow marine cumuli live longer when they cover a larger surface area and show higher cloud optical thickness (COT). Besides the effect of COT, the scale of the atmospheric motions with which the clouds interact is also critical to their lifetime. Plain Language Summary We present a detailed investigation of the lifetime of Caribbean trade‐wind cumulus clouds and the temporal evolution of their physical properties based on geostationary observations with the Advanced Baseline Imager aboard the geostationary GOES‐16 satellite during the “ElUcidating the RolE of Cloud–Circulation Coupling in ClimAte” (EUREC4A) field experiment in winter 2020. The tracking of 2.7 million individual clouds in measurements with high spatio‐temporal resolution enables the investigation of processes that control the lifetime of shallow marine cumulus (SMC) clouds. Our analysis reveals that SMC clouds live longer when they span over a surface area that exceeds an order of tens of square kilometers. While these clouds show similar median cloud droplet size and number concentration compared to shorter‐lived clouds, they contain more liquid water and, thus, show a COT that is increased by about one third. Besides the effect of COT, we find that the scale of the atmospheric motions with which the clouds interact is also critical to their lifetime. Key Points First study of the life cycle of shallow marine cumulus based on observations with the Advanced Baseline Imager aboard GOES‐16 Confirmation of the double power law in the distribution of cloud lifetime from measurements with a temporal resolution of 1 minute Cloud lifetime is related to large‐scale circulation and affects cloud optical thickness

Lysergic acid diethylamide (LSD) is used recreationally and has been evaluated as an adjunct to psychotherapy to treat anxiety in patients with life-threatening illness. LSD is well-known to induce perceptual alterations, but unknown is whether LSD alters emotional processing in ways that can support psychotherapy. We investigated the acute effects of LSD on emotional processing using the Face Emotion Recognition Task (FERT) and Multifaceted Empathy Test (MET). The effects of LSD on social behavior were tested using the Social Value Orientation (SVO) test. Two similar placebo-controlled, double-blind, random-order, crossover studies were conducted using 100 μg LSD in 24 subjects and 200 μg LSD in 16 subjects. All of the subjects were healthy and mostly hallucinogen-naive 25- to 65-year-old volunteers (20 men, 20 women). LSD produced feelings of happiness, trust, closeness to others, enhanced explicit and implicit emotional empathy on the MET, and impaired the recognition of sad and fearful faces on the FERT. LSD enhanced the participants' desire to be with other people and increased their prosocial behavior on the SVO test. These effects of LSD on emotion processing and sociality may be useful for LSD-assisted psychotherapy.

Spaceborne radar altimeters record echo waveforms over all Earth surfaces, but their interpretation and quantitative exploitation over the Arctic Ocean is particularly challenging. Radar returns may be from all ocean, all sea ice, or a mixture of the two, so the first task is the determination of which surface and then an interpretation of the signal to give range. Subsequently, corrections have to be applied for various surface and atmospheric effects before making a comparison with a reference level. This paper discusses the drivers for improved altimetry in the Arctic and then reviews the various approaches that have been used to achieve the initial classification and subsequent retracking over these diverse surfaces, showing examples from both LRM (low resolution mode) and SAR (synthetic aperture radar) altimeters. The review then discusses the issues concerning corrections, including the choices between using other remote-sensing measurements and using those from models or climatology. The paper finishes with some perspectives on future developments, incorporating secondary frequency, interferometric SAR and opportunities for fusion with measurements from laser altimetry or from the SMOS salinity sensor, and provides a full list of relevant abbreviations.

Growing interest has been seen in using lysergic acid diethylamide (LSD) and psilocybin in psychiatric research and therapy. However, no modern studies have evaluated differences in subjective and autonomic effects of LSD and psilocybin or their similarities and dose equivalence. We used a double-blind, randomized, placebo-controlled, crossover design in 28 healthy subjects (14 women, 14 men) who underwent five 25 h sessions and received placebo, LSD (100 and 200 µg), and psilocybin (15 and 30 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales for subjective effects, autonomic effects, adverse effects, effect durations, plasma levels of brain-derived neurotrophic factor (BDNF), prolactin, cortisol, and oxytocin, and pharmacokinetics. The doses of 100 and 200 µg LSD and 30 mg psilocybin produced comparable subjective effects. The 15 mg psilocybin dose produced clearly weaker subjective effects compared with both doses of LSD and 30 mg psilocybin. The 200 µg dose of LSD induced higher ratings of ego-dissolution, impairments in control and cognition, and anxiety than the 100 µg dose. The 200 µg dose of LSD increased only ratings of ineffability significantly more than 30 mg psilocybin. LSD at both doses had clearly longer effect durations than psilocybin. Psilocybin increased blood pressure more than LSD, whereas LSD increased heart rate more than psilocybin. However, both LSD and psilocybin showed comparable cardiostimulant properties, assessed by the rate-pressure product. Both LSD and psilocybin had dose-proportional pharmacokinetics and first-order elimination. Both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. However, LSD and psilocybin differentially increased heart rate and blood pressure. These results may assist with dose finding for future psychedelic research.Trial registration: ClinicalTrials.gov identifier: NCT03604744

Anxiety disorders are a major public health burden with limited treatment options. We investigated the long-term safety and efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with anxiety with or without life-threatening illness. This study was an -planned long-term follow-up of an investigator-initiated, two-centre trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. Participants ( = 39) were followed up 1 year after the end-of-study visit to assess symptoms of anxiety, depression and long-term effects of psychedelics using Spielberger's State-Trait Anxiety Inventory-Global (STAI-G), the Beck Depression Inventory (BDI), the Persisting Effects Questionnaire and measures of personality traits using the NEO Five-Factor Inventory. Participants reported a sustained reduction of STAI-G scores compared with baseline (least square means (95% CI) = -21.6 (-32.7, -10.4), = 1.04, < 0.001, for those who received LSD in the first period (94 weeks after the last LSD treatment) and -16.5 (-26.2, -6.8), = 1.02, < 0.05, for those who received LSD in the second period (68 weeks after the last LSD treatment)). Similar effects were observed for comorbid depression with change from baseline BDI scores of -8.1 (-13.2, -3.1), = 0.71, < 0.01, and -8.9 (-12.9, -4.9), = 1.21, < 0.01, for the LSD-first and placebo-first groups, respectively. Personality trait neuroticism decreased ( < 0.0001) and trait extraversion increased ( < 0.01) compared with study inclusion. Individuals attributed positive long-term effects to the psychedelic experience. Patients reported sustained long-term effects of LSD-assisted therapy for anxiety.

Tracking individual clouds in geostationary satellite observations and numerical simulations allows to quantify cloud lifetime and development. These higher‐dimensional parameters are used in a novel approach to assess the fidelity of cloud‐resolving models. Clouds are tracked in 2 months of satellite observations and accompanying model simulations of trade‐wind cumulus clouds during the EUREC4A campaign. Two Icosahedral Nonhydrostatic Large Eddy Model simulations with different spatial resolution give time series of cloud cover that reasonably resemble the GOES‐16 observations, despite large differences in the number of clouds. Analysis of the tracked clouds yields similar distributions of cloud size, development, and lifetime in line with the expected values for different dynamic regimes from energy cascade theory. However, we find that the model underestimates the occurrence frequency of larger, longer‐lived clouds. This effect is enhanced for finer model resolutions and might be related to the transfer of energy from larger‐scale processes into the domain of the large‐eddy simulation.