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Owing to their short runtime compared to Earth system models (ESMs), as well as the difficulty for the latest ESMs from the Coupled Model Intercomparison Project Phase 6 (CMIP6) to reproduce historical warming and the so-called ‘hot model problem’, constrained reduced-complexity climate models (‘emulators’) are increasingly used to produce global warming projections from emissions scenarios. Emulators are often calibrated on idealised abrupt CO 2 quadrupling experiments from CMIP6, particularly the global surface temperature response over time to an imposed radiative forcing. Such CMIP6 experiments tend to be run for 150 years, which is not sufficient to reveal the full equilibrium response to an imposed climate forcing. Here we show that, when longer experiments are available for emulator calibration, the long-term climate warming projections increase, particularly for 2100, by up to 0.70 (0.42–0.93, 25th to 75th percentile) °C in the median under a high emissions scenario; peak global warming in a high overshoot scenario is higher by 0.24 °C (0.14–0.31 °C). Corresponding long-term thermosteric sea level rise (SLR) is consequently higher, by 0.45 (0.22–0.52, 25th to 75th percentile) m in 2500. This result, consistent across calibrations from 17 ESMs, has implications for climate change mitigation strategies, as it is likely that even more stringent emissions reductions would be required to limit long-term warming and SLR than previously thought.

The climate system responds to changes in the amount of atmospheric greenhouse gases or aerosols through rapid processes, triggered within hours and days, and through slower processes, where the full response may only be seen after centuries. In this paper, we aim to elucidate the mechanisms operating on time scales of hours to years to better understand the response of key climate quantities such as energy fluxes, temperature, and precipitation after a sudden increase in either carbon dioxide (CO2), black carbon (BC), or sulfate (SO4) aerosols. The results are based on idealized simulations from six global climate models. We find that the effect of changing ocean temperatures kicks in after a couple of months. Rapid precipitation reductions start occurring instantly and are established after just a few days. For BC, they constitute most of the equilibrium response. For CO2 and SO4, the magnitude of the precipitation response gradually increases as surface warming/cooling evolves, and for CO2, the sign of the response changes from negative to positive after 2 years. Rapid cloud adjustments are typically established within the first 24 h, and while the magnitude of cloud feedbacks for CO2 and SO4 increases over time, the geographical pattern of the equilibrium cloud change is present already after the first year. While there are model differences, our work underscores the overall similarity of the major time-varying processes and responses simulated by current global models and hence the robustness of key features of simulated responses to historical and future anthropogenic forcing.

RNA polymerases (RNAPs) transcribe genes through a cycle of recruitment to promoter DNA, initiation, elongation, and termination. After termination, RNAP is thought to initiate the next round of transcription by detaching from DNA and rebinding a new promoter. Here we use single-molecule fluorescence microscopy to observe individual RNAP molecules after transcript release at a terminator. Following termination, RNAP almost always remains bound to DNA and sometimes exhibits one-dimensional sliding over thousands of basepairs. Unexpectedly, the DNA-bound RNAP often restarts transcription, usually in reverse direction, thus producing an antisense transcript. Furthermore, we report evidence of this secondary initiation in live cells, using genome-wide RNA sequencing. These findings reveal an alternative transcription cycle that allows RNAP to reinitiate without dissociating from DNA, which is likely to have important implications for gene regulation. In the canonical bacterial transcription, both nascent transcript and polymerase dissociate from template DNA. By employing multi-color single-molecule fluorescence imaging, here the authors show that RNA polymerases remain bound to DNA after the transcript release.

The new global Feedback-based knowledge Repository for IntegrateD Assessments version 2.1 (FRIDAv2.1) Integrated Assessment Model (IAM) seeks to study the dynamics of the coupled human-Earth system. Connecting anthropogenic emissions to the resultant climate response is one part of the two-way feedback within this system, with the resultant climate impacts the other. This paper documents both the Climate Module within FRIDAv2.1, and the modified version separately simulated as a standalone simple climate model termed FRIDA-Clim version 1.0.1. This approach, based loosely on the existing FaIR simple climate model, simulates the key radiative forcings and the resultant temperature response, with process-based representations of the carbon cycle across the ocean, land, and atmosphere. When connected within the FRIDA IAM, it features deep connections to the other modules, being affected by processes such as water use for irrigation and land use change. In both uses, i.e. with the climate response interactively connected to the upstream human drivers and downstream climate impacts within the FRIDA IAM (coupled) and when ran separately as FRIDA-Clim driven by exogenous forcings (uncoupled), its climate drivers are simplified as compared to FaIR. This is to allow for this reduced set of key drivers to be interactively simulated within FRIDA, tightly coupling the evolution of the social and climate systems within the full model. Both the Climate Module and FRIDA-Clim are fully calibrated to accurately reproduce observations of key climate variables, with a systematic exploration of the uncertainty in the climate response. Together with the rest of the FRIDA model, this module is used to incorporate climate change systematically in the FRIDA System Dynamics IAM. As a standalone climate model, FRIDA-Clim comprises a simple climate model, enabling fast calculation of the global climate response to forcing; to explore this, the response of the model to both idealised CO2 emissions experiments and plausible future scenarios is also presented here. This setup will allow FRIDA-Clim to contribute to inter-model simple climate modelling initiatives, helping to explore the structural uncertainty in this modelling domain.

The ability to recognize individuals and track growth over time is crucial to population dynamics research as well as studies of animal behavior. Invertebrates are particularly difficult to track as they often molt, have regenerative capabilities, or lack hard parts to attach markers. We tested, in laboratory and field studies, a new way of marking sea anemones (order Actiniaria) by injection of three vital stains (i.e., neutral red, methylene blue, and fluorescein). Neutral red and methylene blue did not affect growth or survival, but fluorescein was lethal at high concentrations. Marked individuals could be identified up to seven months after injection with neutral red, six weeks with methylene blue, and three days with low concentrations of fluorescein. Neutral red could be used for long-term monitoring of growth and survival in the field, and in combination with methylene blue could be used to mark individuals in distinguishable patterns for short-term studies such as examining predator-prey interactions, movement of individuals, and recruitment survival.

Benthic suspension feeders have significant impacts on plankton communities by depleting plankton or modifying the composition of the plankton through prey selectivity. Quantifying diets of planktivorous animals can be difficult because plankton are frequently microscopic, may lack diagnostic characters, and are digested at variable rates. With DNA metabarcoding, the identification of gut contents has become faster and more accurate, and the technique allows for higher taxonomic resolution while also identifying rare and highly degraded items that would otherwise not be detected. We used DNA metabarcoding to examine the diet of the giant plumose anemone Metridium farcimen, a large, abundant, competitively dominant anemone on subtidal rock surfaces and floating docks in the northeast Pacific Ocean. Gut contents of 12 individuals were compared to 80‐ and 330‐µm filtered plankton samples collected one hour prior between 0.02 and 1.5 km from the anemones. The objectives of this study were to determine if M. farcimen has a selective diet and compare our findings with traditional gut content analyses. Metabarcoding demonstrated that M. farcimen captured a wider range of prey than previously suspected using traditional visual sampling techniques. Individual gut contents had less richness than the 80‐µm filtered plankton samples but had greater richness than the 330‐µm filtered plankton samples. The diet of the anemones was 52% arthropods with a surprisingly high relative abundance of an ant (10%) that has mating flights in August when this study was conducted. The gut contents of M. farcimen likely include all prey that elicit a predation response and that cannot escape. There were no statistically overrepresented taxa in the gut contents compared to the plankton but there were underrepresented taxa. This study highlights the usefulness of the metabarcoding method in identifying prey within the gut of planktivorous animals and the significant terrestrial input into marine food webs. The diet of the competitively dominant and abundant sea anemone Metridium farcimen was compared with available food within the plankton. Metabarcoding showed that these animals captures a wider range of prey than previously suspected based on conventional visual analysis, including terrestrial invertebrates.

The efficacy of drugs for neuropathic pain has been established in randomized controlled trials that have excluded patients with comorbid conditions and those taking complex medications. However, patients with neuropathic pain frequently present with complex histories, making direct application of this evidence problematic. Treatment of neuropathic pain needs to be individualized according to the cause of the pain, concomitant diseases, medications, and other individual factors. Tricyclic antidepressants (TCAs), gabapentinoids, selective noradrenergic reuptake inhibitors, and topical lidocaine are the first-line choices; if needed, combination therapy may be used. When a new drug is added, screening for potential drug interactions is recommended. The TCAs have anticholinergic adverse effects and may cause orthostatic hypotension. They should be avoided or used cautiously in patients with cardiac conduction disturbances or arrhythmias. Patients who lack cytochrome P450 2D6 isoenzyme activity are prone to adverse effects of TCAs and venlafaxine and have a weaker analgesic response to tramadol. A combination of several serotoninergic drugs may lead to serotonin syndrome. Risk of gastrointestinal tract bleeding is increased in patients taking selective serotonin reuptake inhibitors or venlafaxine, especially when combined with nonsteroidal anti-inflammatory drugs. Dose adjustment may be needed in patients with renal or hepatic impairment. Depending on the drug, the dose is reduced or the dosage interval lengthened. Slow titration and careful follow-up are needed. No drug is absolutely safe during pregnancy and lactation. Particular care must be exercised during the first trimester when drug dose should be as low as possible. Individual weighing of benefits and risks should guide therapeutic decisions.

The optimal interval of imaging studies for surveillance of incidental pancreatic cystic neoplasms is not known. A retrospective analysis of longitudinal medical records of patients with pancreatic cystic neoplasms was performed to examine the natural history of incidentally detected cystic pancreatic neoplasms with respect to the development of significant growth and to identify predictors of such growth. After excluding patients with small (<10 mm) cysts (N = 144) and inadequate clinical follow-up of less than 6 months (N = 79) and those with a clinical diagnosis of pancreatic pseudocysts, serous cystadenoma, main duct intraductal papillary mucinous neoplasm (N = 29), and neuroendocrine tumor (N = 3), in total, 166 cysts in 150 patients were available for analysis. The working diagnoses on these cysts (based on clinical, radiological features, aspiration cytology, cyst fluid analysis, and surgical pathology data when available) were mucinous cystic neoplasm in 117 and branch-type intraductal papillary mucinous neoplasm in 49. The mean standard error (SE) initial size of these cysts was 2 (0.1) cm. Over a median period of follow-up of 32 (IQR [inter-quartile range] 19-48) months, 89% of all the cysts did not show significant growth during the follow-up. In a multivariate Cox proportional hazards model, the initial size of the cystic lesion was an independent predictor of significant growth during follow-up (relative risk 1.28, 95% confidence interval [CI] 1.08-1.61, P= 0.01); the only other significant variable was the presence of intracystic or mural nodule (relative risk 38.6, 95% CI 2.3-654, P= 0.01). Most incidentally detected cystic neoplasms of the pancreas did not have significant growth during follow-up. Such growth is unlikely to occur before 2 yr of the baseline evaluation, and we suggest that the optimal imaging interval during follow-up of these patients should be at 2 yr from the baseline evaluation, particularly in cystic lesions 3.0 cm or less in size and without intracystic or mural nodules.

The σ subunit of bacterial RNA polymerase (RNAP) confers on the enzyme the ability to initiate promoter-specific transcription. Although σ factors are generally classified as initiation factors, σ can also remain associated with, and modulate the behavior of, RNAP during elongation. Here we establish that the primary σ factor in Escherichia coli, σ70, can function as an elongation factor in vivo by loading directly onto the transcription elongation complex (TEC) in trans. We demonstrate that σ70 can bind in trans to TECs that emanate from either a σ70-dependent promoter or a promoter that is controlled by an alternative σ factor. We further demonstrate that binding of σ70 to the TEC in trans can have a particularly large impact on the dynamics of transcription elongation during stationary phase. Our findings establish a mechanism whereby the primary σ factor can exert direct effects on the composition of the entire transcriptome, not just that portion that is produced under the control of σ70-dependent promoters. Proteins are made following instructions that are encoded by sections of DNA called genes. In the first step of protein production, an enzyme called RNA polymerase uses the gene as a template to make molecules of messenger ribonucleic acid (mRNA). This process—known as transcription—starts when RNA polymerase binds to a site at the start of a gene. The enzyme then moves along the DNA, assembling the mRNA as it goes. This stage of transcription is known as elongation and continues until the RNA polymerase reaches the end of the gene. In bacteria, RNA polymerase needs a family of proteins called sigma factors to help it identify and bind to the start sites associated with the genes that will be transcribed. In the well studied bacterium known as E. coli, the primary sigma factor that is required for transcription initiation on most genes is called sigma 70. Recent research has shown that sigma 70 also influences the activity of RNA polymerase during elongation. During this stage, the RNA polymerase and several other proteins interact to form a complex called the transcription elongation complex (or TEC for short). However, it is not clear how sigma 70 gains access to this complex: does it simply remain with RNA polymerase after transcription starts, or is it freshly incorporated into the TEC during elongation? Goldman, Nair et al. found that sigma 70 is able to incorporate into TECs during elongation and causes them to pause at specific sites in the gene. Sigma 70 can even incorporate into TECs on genes where transcription was initiated by a different sigma factor. These findings indicate that sigma 70 can directly influence the transcription of all genes, not just the genes with start sites that are recognized by this sigma factor. Goldman et al. also observed that in cells that were growing and dividing rapidly, the pauses that occurred due to sigma 70 associating with TECs were of shorter duration than those in cells that were growing slowly. This implies that the growth status of the cells modulates the pausing of RNA polymerase during transcription. In the future, it will be important to understand how much influence the primary sigma factor has on RNA polymerase during elongation in E. coli and other bacteria.

The potential future trend in African aerosol emissions is uncertain, with a large range found in future scenarios used to drive climate projections. The future climate impact of these emissions is therefore uncertain. Using the Shared Socioeconomic Pathway (SSP) scenarios, transient future experiments were performed with the UK Earth System Model (UKESM1) to investigate the effect of African emissions following the high emission SSP370 scenario as the rest of the world follows the more sustainable SSP119, relative to a global SSP119 control. This isolates the effect of Africa following a relatively more polluted future emissions pathway. Compared to SSP119, SSP370 projects higher non-biomass-burning (non-BB) aerosol emissions, but lower biomass burning emissions, over Africa. Increased shortwave (SW) absorption by black carbon aerosol leads to a global warming, but the reduction in the local incident surface radiation close to the emissions is larger, causing a local cooling effect. The local cooling persists even when including the higher African CO2 emissions under SSP370 than SSP119. The global warming is significantly higher by 0.07 K when including the non-BB aerosol increases and higher still (0.22 K) when including all aerosols and CO2. Precipitation also exhibits complex changes. Northward shifts in the Inter-tropical Convergence Zone (ITCZ) occur under relatively warm Northern Hemisphere land, and local rainfall is enhanced due to mid-tropospheric instability from black carbon absorption. These results highlight the importance of future African aerosol emissions for regional and global climate and the spatial complexity of this climate influence.