Suppressed basal melting in the eastern Thwaites Glacier grounding zone.

Thwaites Glacier is one of the fastest-changing ice-ocean systems in Antarctica1-3. Much of the ice sheet within the catchment of Thwaites Glacier is grounded below sea level on bedrock that deepens inland4, making it susceptible to rapid and irreversible ice loss that could raise the global sea level by more than half a metre2,3,5. The rate and extent of ice loss, and whether it proceeds irreversibly, are set by the ocean conditions and basal melting within the grounding-zone region where Thwaites Glacier first goes afloat3,6, both of which are largely unknown. Here we show-using observations from a hot-water-drilled access hole-that the grounding zone of Thwaites Eastern Ice Shelf (TEIS) is characterized by a warm and highly stable water column with temperatures substantially higher than the in situ freezing point. Despite these warm conditions, low current speeds and strong density stratification in the ice-ocean boundary layer actively restrict the vertical mixing of heat towards the ice base7,8, resulting in strongly suppressed basal melting. Our results demonstrate that the canonical model of ice-shelf basal melting used to generate sea-level projections cannot reproduce observed melt rates beneath this critically important glacier, and that rapid and possibly unstable grounding-line retreat may be associated with relatively modest basal melt rates.

Decoding myofibroblast origins in human kidney fibrosis.

Kidney fibrosis is the hallmark of chronic kidney disease progression; however, at present no antifibrotic therapies exist1-3. The origin, functional heterogeneity and regulation of scar-forming cells that occur during human kidney fibrosis remain poorly understood1,2,4. Here, using single-cell RNA sequencing, we profiled the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys to map the entire human kidney. This analysis enabled us to map all matrix-producing cells at high resolution, and to identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single-cell RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin using sequencing) experiments in mice, and spatial transcriptomics in human kidney fibrosis, to shed light on the cellular origins and differentiation of human kidney myofibroblasts and their precursors at high resolution. Finally, we used this strategy to detect potential therapeutic targets, and identified NKD2 as a myofibroblast-specific target in human kidney fibrosis.

Transoceanic pathogen transfer in the age of sail and steam.

In the centuries following Christopher Columbus's 1492 voyage to the Americas, transoceanic travel opened unprecedented pathways in global pathogen circulation. Yet no biological transfer is a single, discrete event. We use mathematical modeling to quantify historical risk of shipborne pathogen introduction, exploring the respective contributions of journey time, ship size, population susceptibility, transmission intensity, density dependence, and pathogen biology. We contextualize our results using port arrivals data from San Francisco, 1850 to 1852, and from a selection of historically significant voyages, 1492 to 1918. We offer numerical estimates of introduction risk across historically realistic ranges of journey time and ship population size, and show that both steam travel and shipping regimes that involved frequent, large-scale movement of people substantially increased risk of transoceanic pathogen circulation.

Automotive braking is a source of highly charged aerosol particles.

Although the last several decades have seen a dramatic reduction in emissions from vehicular exhaust, nonexhaust emissions (e.g., brake and tire wear) represent an increasingly significant class of traffic-related particulate pollution. Aerosol particles emitted from the wear of automotive brake pads contribute roughly half of the particle mass attributed to nonexhaust sources, while their relative contribution to urban air pollution overall will almost certainly grow coinciding with vehicle fleet electrification and the transition to alternative fuels. To better understand the implications of this growing prominence, a more thorough understanding of the physicochemical properties of brake wear particles (BWPs) is needed. Here, we investigate the electrical properties of BWPs as emitted from ceramic and semi-metallic brake pads. We show that up to 80% of BWPs emitted are electrically charged and that this fraction is strongly dependent on the specific brake pad material used. A dependence of the number of charges per particle on charge polarity and particle size is also demonstrated. We find that brake wear produces both positive and negative charged particles that can hold in excess of 30 elementary charges and show evidence that more negative charges are produced than positive. Our results will provide insights into the currently limited understanding of BWPs and their charging mechanisms, which potentially have significant implications on their atmospheric lifetimes and thus their relevance to climate and air quality. In addition, our study will inform future efforts to remove BWP emissions before entering the atmosphere by taking advantage of their electric charge.

Synchronous retreat of Thwaites and Pine Island glaciers in response to external forcings in the presatellite era.

Today, relatively warm Circumpolar Deep Water is melting Thwaites Glacier at the base of its ice shelf and at the grounding zone, contributing to significant ice retreat. Accelerating ice loss has been observed since the 1970s; however, it is unclear when this phase of significant melting initiated. We analyzed the marine sedimentary record to reconstruct Thwaites Glacier's history from the early Holocene to present. Marine geophysical surveys were carried out along the floating ice-shelf margin to identify core locations from various geomorphic settings. We use sedimentological data and physical properties to define sedimentary facies at seven core sites. Glaciomarine sediment deposits reveal that the grounded ice in the Amundsen Sea Embayment had already retreated to within ~45 km of the modern grounding zone prior to ca. 9,400 y ago. Sediments deposited within the past 100+ y record abrupt changes in environmental conditions. On seafloor highs, these shifts document ice-shelf thinning initiating at least as early as the 1940s. Sediments recovered from deep basins reflect a transition from ice proximal to slightly more distal conditions, suggesting ongoing grounding-zone retreat since the 1950s. The timing of ice-shelf unpinning from the seafloor for Thwaites Glacier coincides with similar records from neighboring Pine Island Glacier. Our work provides robust new evidence that glacier retreat in the Amundsen Sea was initiated in the mid-twentieth century, likely associated with climate variability.

Predicting the presence of infectious virus from PCR data: A meta-analysis of SARS-CoV-2 in non-human primates.

Researchers and clinicians often rely on molecular assays like PCR to identify and monitor viral infections, instead of the resource-prohibitive gold standard of viral culture. However, it remains unclear when (if ever) PCR measurements of viral load are reliable indicators of replicating or infectious virus. The recent popularity of PCR protocols targeting subgenomic RNA for SARS-CoV-2 has caused further confusion, as the relationships between subgenomic RNA and standard total RNA assays are incompletely characterized and opinions differ on which RNA type better predicts culture outcomes. Here, we explore these issues by comparing total RNA, subgenomic RNA, and viral culture results from 24 studies of SARS-CoV-2 in non-human primates (including 2167 samples from 174 individuals) using custom-developed Bayesian statistical models. On out-of-sample data, our best models predict subgenomic RNA positivity from total RNA data with 91% accuracy, and they predict culture positivity with 85% accuracy. Further analyses of individual time series indicate that many apparent prediction errors may arise from issues with assay sensitivity or sample processing, suggesting true accuracy may be higher than these estimates. Total RNA and subgenomic RNA showed equivalent performance as predictors of culture positivity. Multiple cofactors (including exposure conditions, host traits, and assay protocols) influence culture predictions, yielding insights into biological and methodological sources of variation in assay outcomes-and indicating that no single threshold value applies across study designs. We also show that our model can accurately predict when an individual is no longer infectious, illustrating the potential for future models trained on human data to guide clinical decisions on case isolation. Our work shows that meta-analysis of in vivo data can overcome longstanding challenges arising from limited sample sizes and can yield robust insights beyond those attainable from individual studies. Our analytical pipeline offers a framework to develop similar predictive tools in other virus-host systems, including models trained on human data, which could support laboratory analyses, medical decisions, and public health guidelines.

Temperate rainforests near the South Pole during peak Cretaceous warmth.

The mid-Cretaceous period was one of the warmest intervals of the past 140 million years1-5, driven by atmospheric carbon dioxide levels of around 1,000 parts per million by volume6. In the near absence of proximal geological records from south of the Antarctic Circle, it is disputed whether polar ice could exist under such environmental conditions. Here we use a sedimentary sequence recovered from the West Antarctic shelf-the southernmost Cretaceous record reported so far-and show that a temperate lowland rainforest environment existed at a palaeolatitude of about 82° S during the Turonian-Santonian age (92 to 83 million years ago). This record contains an intact 3-metre-long network of in situ fossil roots embedded in a mudstone matrix containing diverse pollen and spores. A climate model simulation shows that the reconstructed temperate climate at this high latitude requires a combination of both atmospheric carbon dioxide concentrations of 1,120-1,680 parts per million by volume and a vegetated land surface without major Antarctic glaciation, highlighting the important cooling effect exerted by ice albedo under high levels of atmospheric carbon dioxide.

Biosecurity in an age of open science.

The risk of accidental or deliberate misuse of biological research is increasing as biotechnology advances. As open science becomes widespread, we must consider its impact on those risks and develop solutions that ensure security while facilitating scientific progress. Here, we examine the interaction between open science practices and biosecurity and biosafety to identify risks and opportunities for risk mitigation. Increasing the availability of computational tools, datasets, and protocols could increase risks from research with misuse potential. For instance, in the context of viral engineering, open code, data, and materials may increase the risk of release of enhanced pathogens. For this dangerous subset of research, both open science and biosecurity goals may be achieved by using access-controlled repositories or application programming interfaces. While preprints accelerate dissemination of findings, their increased use could challenge strategies for risk mitigation at the publication stage. This highlights the importance of oversight earlier in the research lifecycle. Preregistration of research, a practice promoted by the open science community, provides an opportunity for achieving biosecurity risk assessment at the conception of research. Open science and biosecurity experts have an important role to play in enabling responsible research with maximal societal benefit.

Lipophilic Statins Inhibit YAP Nuclear Localization, Coactivator Activity, and Migration in Response to Ligation of HLA Class I Molecules in Endothelial Cells: Role of YAP Multisite Phosphorylation.

Solid-organ transplant recipients exhibiting HLA donor-specific Abs are at risk for graft loss due to chronic Ab-mediated rejection. HLA Abs bind HLA molecules expressed on the surface of endothelial cells (ECs) and induce intracellular signaling pathways, including the activation of the transcriptional coactivator yes-associated protein (YAP). In this study, we examined the impact of lipid-lowering drugs of the statin family on YAP localization, multisite phosphorylation, and transcriptional activity in human ECs. Exposure of sparse cultures of ECs to cerivastatin or simvastatin induced striking relocalization of YAP from the nucleus to the cytoplasm and inhibited the expression of the YAP/TEA domain DNA-binding transcription factor-regulated genes connective tissue growth factor and cysteine-rich angiogenic inducer 61. In dense cultures of ECs, statins prevented YAP nuclear import and expression of connective tissue growth factor and cysteine-rich angiogenic inducer 61 stimulated by the mAb W6/32 that binds HLA class I. Exposure of ECs to either cerivastatin or simvastatin completely blocked the migration of ECs stimulated by ligation of HLA class I. Exogenously supplied mevalonic acid or geranylgeraniol reversed the inhibitory effects of statins on YAP localization either in low-density ECs or high-density ECs challenged with W6/32. Mechanistically, cerivastatin increased the phosphorylation of YAP at Ser127, blunted the assembly of actin stress fiber, and inhibited YAP phosphorylation at Tyr357 in ECs. Using mutant YAP, we substantiated that YAP phosphorylation at Tyr357 is critical for YAP activation. Collectively, our results indicate that statins restrain YAP activity in EC models, thus providing a plausible mechanism underlying their beneficial effects in solid-organ transplant recipients.

Trade-offs between bycatch and target catches in static versus dynamic fishery closures.

While there have been recent improvements in reducing bycatch in many fisheries, bycatch remains a threat for numerous species around the globe. Static spatial and temporal closures are used in many places as a tool to reduce bycatch. However, their effectiveness in achieving this goal is uncertain, particularly for highly mobile species. We evaluated evidence for the effects of temporal, static, and dynamic area closures on the bycatch and target catch of 15 fisheries around the world. Assuming perfect knowledge of where the catch and bycatch occurs and a closure of 30% of the fishing area, we found that dynamic area closures could reduce bycatch by an average of 57% without sacrificing catch of target species, compared to 16% reductions in bycatch achievable by static closures. The degree of bycatch reduction achievable for a certain quantity of target catch was related to the correlation in space and time between target and bycatch species. If the correlation was high, it was harder to find an area to reduce bycatch without sacrificing catch of target species. If the goal of spatial closures is to reduce bycatch, our results suggest that dynamic management provides substantially better outcomes than classic static marine area closures. The use of dynamic ocean management might be difficult to implement and enforce in many regions. Nevertheless, dynamic approaches will be increasingly valuable as climate change drives species and fisheries into new habitats or extended ranges, altering species-fishery interactions and underscoring the need for more responsive and flexible regulatory mechanisms.

Extended Postexposure Protection Against Vaginal Simian/Human Immunodeficiency Virus Infection With Tenofovir Alafenamide Fumarate/Elvitegravir Inserts in Macaques.

Vaginal inserts that can be used on demand before or after sex may be a desirable human immunodeficiency virus (HIV) prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF, 20 mg) and elvitegravir (EVG, 16 mg) were highly protective against repeated simian/human immunodeficiency virus (SHIV) vaginal exposures when administered to macaques 4 hours before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8 hours or 24 hours after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.

The FAM13A Long Isoform Regulates Cilia Movement and Co-ordination in Airway Mucociliary Transport.

SNPs in the FAM13A locus are amongst the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases, however the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the FAM13A locus: 'long' and 'short', but their functions remain unknown, partly due to a lack of isoform conservation in mice. We performed in-depth characterisation of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase activating protein (RhoGAP) domain. Using purified proteins, we directly demonstrate RhoGAP activity of this domain. In Xenopus laevis, which conserve the long isoform, Fam13a-deficiency impaired cilia-dependent embryo motility. In human primary epithelial cells, long isoform deficiency did not affect multiciliogenesis but reduced cilia co-ordination in mucociliary transport assays. This is the first demonstration that FAM13A isoforms are differentially expressed within the airway epithelium, with implications for the assessment and interpretation of SNP effects on FAM13A expression levels. We also show that the long FAM13A isoform co-ordinates cilia-driven movement, suggesting that FAM13A risk alleles may affect susceptibility to respiratory diseases through deficiencies in mucociliary clearance. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Adjunct Immune Globulin for Vaccine-Induced Immune Thrombotic Thrombocytopenia.

The use of high-dose intravenous immune globulin (IVIG) plus anticoagulation is recommended for the treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare side effect of adenoviral vector vaccines against coronavirus disease 2019 (Covid-19). We describe the response to IVIG therapy in three of the first patients in whom VITT was identified in Canada after the receipt of the ChAdOx1 nCoV-19 vaccine. The patients were between the ages of 63 and 72 years; one was female. At the time of this report, Canada had restricted the use of the ChAdOx1 nCoV-19 vaccine to persons who were 55 years of age or older on the basis of reports that VITT had occurred primarily in younger persons. Two of the patients in our study presented with limb-artery thrombosis; the third had cerebral venous and arterial thrombosis. Variable patterns of serum-induced platelet activation were observed in response to heparin and platelet factor 4 (PF4), indicating the heterogeneity of the manifestations of VITT in serum. After the initiation of IVIG, reduced antibody-induced platelet activation in serum was seen in all three patients. (Funded by the Canadian Institutes of Health Research.).

Pancreatic exocrine insufficiency after non-pancreatic upper gastrointestinal surgery: meta-analysis.

BACKGROUND: Untreated pancreatic exocrine insufficiency (PEI) results in substantial patient harm. Upper gastrointestinal surgery (bariatric metabolic surgery and oesophagogastric resection) affects the delicate physiology of pancreatic exocrine function and may result in PEI. The aim of this study was to assimilate the literature on incidence, diagnosis, and management of PEI after bariatric metabolic surgery and oesophagogastric resection. METHODS: A systematic review of PubMed, MEDLINE, and Embase databases identified studies investigating PEI after non-pancreatic upper gastrointestinal surgery. Meta-analyses were undertaken for incidence of PEI and benefit of pancreatic enzyme replacement therapy. RESULTS: Among 1620 patients from 24 studies included in quantitative synthesis, 36.0% developed PEI. The incidence of PEI was 23.0 and 50.4% after bariatric metabolic surgery and oesophagogastric resection respectively. Notably, the incidence of PEI was 44% after biliopancreatic diversion with duodenal switch and 66.2% after total gastrectomy. The most common diagnostic test used was faecal elastase 1 (15 of 31 studies), with less than 200 µg/g being diagnostic of PEI. A total of 11 studies considered the management of pancreatic exocrine insufficiency, with 78.6% of patients responding positively to pancreatic enzyme replacement when it was prescribed. CONCLUSION: PEI is common after non-pancreatic upper gastrointestinal surgery and patients may benefit from enzyme replacement therapy.

Pancreatic exocrine insufficiency occurs when enzymes from the pancreas are unable to help digest food. Pancreatic exocrine insufficiency is known to cause disruptive symptoms after gastrointestinal surgery. Although such symptoms are well known after pancreatic surgery, after other gastrointestinal operations, including bariatric metabolic surgery and oesophagogastric cancer resection, pancreatic exocrine insufficiency is often overlooked as a cause of both symptoms and poor nutrition. This study looked at, and combined, all the current evidence on the rate of pancreatic exocrine insufficiency after these operations, the way it is diagnosed, and how it is treated. Pancreatic exocrine insufficiency may be more common than previously thought after bariatric metabolic surgery or oesophagogastric surgery, and clinicians working with these patients should have a low threshold for starting treatment.

Identification of QTLs for symbiotic nitrogen fixation and related traits in a soybean recombinant inbred line population.

KEY MESSAGE: The genetic architecture of symbiotic N fixation and related traits was investigated in the field. QTLs were identified for percent N derived from the atmosphere, shoot [N] and C to N ratio. Soybean [Glycine max (L.) Merr.] is cultivated worldwide and is the most abundant source of plant-based protein. Symbiotic N2 fixation (SNF) in legumes such as soybean is of great importance; however, yields may still be limited by N in both high yielding and stressful environments. To better understand the genetic architecture of SNF and facilitate the development of high yielding cultivars and sustainable soybean production in stressful environments, a recombinant inbred line population consisting of 190 lines, developed from a cross between PI 442012A and PI 404199, was evaluated for N derived from the atmosphere (Ndfa), N concentration ([N]), and C to N ratio (C/N) in three environments. Significant genotype, environment and genotype × environment effects were observed for all three traits. A linkage map was constructed containing 3309 single nucleotide polymorphism (SNP) markers. QTL analysis was performed for additive effects of QTLs, QTL × environment interactions, and QTL × QTL interactions. Ten unique additive QTLs were identified across all traits and environments. Of these, two QTLs were detected for Ndfa and eight for C/N. Of the eight QTLs for C/N, four were also detected for [N]. Using QTL × environment analysis, six QTLs were detected, of which five were also identified in the additive QTL analysis. The QTL × QTL analysis identified four unique epistatic interactions. The results of this study may be used for genomic selection and introgression of favorable alleles for increased SNF, [N], and C/N via marker-assisted selection.

Comprehensive, long-term evaluation of pancreatic exocrine insufficiency after pancreatoduodenectomy.

AIMS: Treatment of pancreatic exocrine insufficiency (PEI) following pancreatoduodenectomy (PD) improves quality of life, clinical outcomes, and survival. However, diagnosing PEI following PD is challenging owing to the difficulties with current tests and often non-specific symptoms. This work aims to quantify the true rate of long-term PEI in patients following a PD. METHODS: Patients underwent a PEI screen approximately one to two years following PD for oncologic indication, including the 13C Mixed triglyceride breath test (13CMTGT), faecal elastase 1 (FE-1) and the PEI Questionnaire (PEI-Q). Four reviewers with expertise in PEI reviewed the results blinded to other decisions to classify PEI status; disagreements were resolved on consensus. RESULTS: 26 patients were recruited. Of those with valid test results, these were indicative of PEI based on pre-specified thresholds for 60 % (15/25) for the 13CMTGT, 82 % (18/22) for FE-1, and 88 % (22/25) for the PEI-Q. After discussion between reviewers, the consensus PEI prevalence was 81 % (95 % CI: 61-93 %; 21/26), with 50 % (N = 13) classified as having severe, 23 % (N = 6) moderate, and 8 % (N = 2) mild PEI. DISCUSSION: Since no ideal test exists for PEI, this collation of diagnostic modalities and blinded expert review was designed to ascertain the true rate of long-term PEI following PD. This required our cohort to survive a year, travel to hospital, and undergo a period of starvation and PERT hold, and therefore there is likely to be recruitment bias towards fitter, younger patients with less aggressive pathology. Despite this, over 80 % were deemed to have PEI, with over 90 % of these being considered moderate or severe.

Ventricular, atrial, and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak.

The heart develops from 2 sources of mesoderm progenitors, the first and second heart field (FHF and SHF). Using a single-cell transcriptomic assay combined with genetic lineage tracing and live imaging, we find the FHF and SHF are subdivided into distinct pools of progenitors in gastrulating mouse embryos at earlier stages than previously thought. Each subpopulation has a distinct origin in the primitive streak. The first progenitors to leave the primitive streak contribute to the left ventricle, shortly after right ventricle progenitor emigrate, followed by the outflow tract and atrial progenitors. Moreover, a subset of atrial progenitors are gradually incorporated in posterior locations of the FHF. Although cells allocated to the outflow tract and atrium leave the primitive streak at a similar stage, they arise from different regions. Outflow tract cells originate from distal locations in the primitive streak while atrial progenitors are positioned more proximally. Moreover, single-cell RNA sequencing demonstrates that the primitive streak cells contributing to the ventricles have a distinct molecular signature from those forming the outflow tract and atrium. We conclude that cardiac progenitors are prepatterned within the primitive streak and this prefigures their allocation to distinct anatomical structures of the heart. Together, our data provide a new molecular and spatial map of mammalian cardiac progenitors that will support future studies of heart development, function, and disease.

Ten simple rules for implementing open and reproducible research practices after attending a training course.

Open, reproducible, and replicable research practices are a fundamental part of science. Training is often organized on a grassroots level, offered by early career researchers, for early career researchers. Buffet style courses that cover many topics can inspire participants to try new things; however, they can also be overwhelming. Participants who want to implement new practices may not know where to start once they return to their research team. We describe ten simple rules to guide participants of relevant training courses in implementing robust research practices in their own projects, once they return to their research group. This includes (1) prioritizing and planning which practices to implement, which involves obtaining support and convincing others involved in the research project of the added value of implementing new practices; (2) managing problems that arise during implementation; and (3) making reproducible research and open science practices an integral part of a future research career. We also outline strategies that course organizers can use to prepare participants for implementation and support them during this process.

The Significant Role of New Particle Composition and Morphology on the HNO3-Driven Growth of Particles down to Sub-10 nm.

New particle formation and growth greatly influence air quality and the global climate. Recent CERN Cosmics Leaving OUtdoor Droplets (CLOUD) chamber experiments proposed that in cold urban atmospheres with highly supersaturated HNO3 and NH3, newly formed sub-10 nm nanoparticles can grow rapidly (up to 1000 nm h-1). Here, we present direct observational evidence that in winter Beijing with persistent highly supersaturated HNO3 and NH3, nitrate contributed less than ∼14% of the 8-40 nm nanoparticle composition, and overall growth rates were only ∼0.8-5 nm h-1. To explain the observed growth rates and particulate nitrate fraction, the effective mass accommodation coefficient of HNO3 (αHNO3) on the nanoparticles in urban Beijing needs to be 2-4 orders of magnitude lower than those in the CLOUD chamber. We propose that the inefficient uptake of HNO3 on nanoparticles is mainly due to the much higher particulate organic fraction and lower relative humidity in urban Beijing. To quantitatively reproduce the observed growth, we show that an inhomogeneous "inorganic core-organic shell" nanoparticle morphology might exist for nanoparticles in Beijing. This study emphasized that growth for nanoparticles down to sub-10 nm was largely influenced by their composition, which was previously ignored and should be considered in future studies on nanoparticle growth.