A decadal satellite record of gravity wave activity in the lower stratosphere to study polar stratospheric cloud formation

Atmospheric gravity waves yield substantial small-scale temperature fluctuations that can trigger the formation of polar stratospheric clouds (PSCs). This paper introduces a new satellite record of gravity wave activity in the polar lower stratosphere to investigate this process. The record is comprised of observations of the Atmospheric Infrared Sounder (AIRS) aboard NASA's Aqua satellite from January 2003 to December 2012. Gravity wave activity is measured in terms of detrended and noise-corrected 15 µm brightness temperature variances, which are calculated from AIRS channels that are the most sensitive to temperature fluctuations at about 17–32 km of altitude. The analysis of temporal patterns in the data set revealed a strong seasonal cycle in wave activity with wintertime maxima at mid- and high latitudes. The analysis of spatial patterns indicated that orography as well as jet and storm sources are the main causes of the observed waves. Wave activity is closely correlated with 30 hPa zonal winds, which is attributed to the AIRS observational filter. We used the new data set to evaluate explicitly resolved temperature fluctuations due to gravity waves in the European Centre for Medium-Range Weather Forecasts (ECMWF) operational analysis. It was found that the analysis reproduces orographic and non-orographic wave patterns in the right places, but that wave amplitudes are typically underestimated by a factor of 2–3. Furthermore, in a first survey of joint AIRS and Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) satellite observations, nearly 50 gravity-wave-induced PSC formation events were identified. The survey shows that the new AIRS data set can help to better identify such events and more generally highlights the importance of the process for polar ozone chemistry

A decadal satellite record of gravity wave activity in the lower stratosphere to study polar stratospheric cloud formation

Atmospheric gravity waves yield substantial small-scale temperature fluctuations that can trigger the formation of polar stratospheric clouds (PSCs). This paper introduces a new satellite record of gravity wave activity in the polar lower stratosphere to investigate this process. The record comprises observations of the Atmospheric InfraRed Sounder (AIRS) aboard NASA's Aqua satellite during January 2003 to December 2012. Gravity wave activity is measured in terms of detrended and noise-corrected 15 μm brightness temperature variances, which are calculated from AIRS channels that are most sensitive to temperature fluctuations at about 17–32 km altitude. The analysis of temporal patterns in the data set revealed a strong seasonal cycle in wave activity with wintertime maxima at mid and high latitudes. The analysis of spatial patterns indicated that orography as well as jet and storm sources are the main cause of the observed waves. Wave activity is closely correlated with 30 hPa zonal winds, which is attributed to the AIRS observational filter. We used the new data set to evaluate explicitly resolved temperature fluctuations due to gravity waves in the European Centre for Medium-Range Weather Forecast (ECMWF) operational analysis. It was found that the analysis reproduces orographic and non-orographic wave patterns in the right places, but that wave amplitudes are typically underestimated by a factor of 2–3. Furthermore, in a first survey of joint AIRS and Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) satellite observations nearly 50 gravity wave-induced PSC formation events were identified. The survey shows that the new AIRS data set can help to better identify such events and more generally highlights the importance of the process for polar ozone chemistry

Observed and Modeled Mountain Waves from the Surface to the Mesosphere Near the Drake Passage

Four state-of-the-science numerical weather prediction (NWP) models were used to perform mountain wave- (MW) resolving hind-casts over the Drake Passage of a 10-day period in 2010 with numerous observed MW cases. The Integrated Forecast System (IFS) and the Icosahedral Nonhydrostatic (ICON) model were run at Δx ≈ 9 and 13 km globally. TheWeather Research and Forecasting (WRF) model and the Met Office Unified Model (UM) were both configured with a Δx = 3 km regional domain. All domains had tops near 1 Pa (z ≈ 80 km). These deep domains allowed quantitative validation against Atmospheric InfraRed Sounder (AIRS) observations, accounting for observation time, viewing geometry, and radiative transfer. All models reproduced observed middle-atmosphere MWs with remarkable skill. Increased horizontal resolution improved validations. Still, all models underrepresented observed MW amplitudes, even after accounting for model effective resolution and instrument noise, suggesting even at Δx ≈ 3 km resolution, small-scale MWs are under-resolved and/or over-diffused. MWdrag parameterizations are still necessary in NWP models at current operational resolutions of Δx ≈ 10 km. Upper GW sponge layers in the operationally configured models significantly, artificially reduced MW amplitudes in the upper stratosphere and mesosphere. In the IFS, parameterized GW drags partly compensated this deficiency, but still, total drags were ≈ 6 time smaller than that resolved at Δx ≈ 3 km. Meridionally propagating MWs significantly enhance zonal drag over the Drake Passage. Interestingly, drag associated with meridional fluxes of zonal momentum (i.e. u'v') were important; not accounting for these terms results in a drag in the wrong direction at and below the polar night jet

The RNA workbench: Best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis

Safety and efficacy of mTOR inhibitor treatment in patients with tuberous sclerosis complex under 2 years of age – a multicenter retrospective study

Background: Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. Results: A total of 17 children (median age at study inclusion 2.4 years, range 0–6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0–19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1–2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3–4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. Conclusion: This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy

Identification and characterization of secreted and pathogenesis-related proteins in Ustilago maydis

Interactions between plants and fungal pathogens require a complex interplay at the plant–fungus interface. Extracellular effector proteins are thought to play a crucial role in establishing a successful infection. To identify pathogenesis-related proteins in Ustilago maydis we combined the isolation of secreted proteins using a signal sequence trap approach with bioinformatic analyses and the subsequent characterization of knock-out mutants. We identified 29 secreted proteins including hydrophobins and proteins with a repetitive structure similar to the repellent protein Rep1. Hum3, a protein containing both, a hydrophobin domain and a repetitive Rep1-like region, is shown to be processed during passage through the secretory pathway. While single knock-outs of hydrophobin or repellent-like genes did not affect pathogenicity, we found a strong effect of a double knock-out of hum3 and the repetitive rsp1. Yeast-like growth, mating, aerial hyphae formation and surface hydrophobicity were unaffected in this double mutant. However, pathogenic development in planta stops early after penetration leading to a complete loss of pathogenicity. This indicates that Hum3 and Rsp1 are pathogenicity proteins that share an essential function in early stages of the infection. Our results demonstrate that focusing on secreted proteins is a promising way to discover novel pathogenicity proteins that might be broadly applied to a variety of fungal pathogens

C. elegans ATAD-3 Is Essential for Mitochondrial Activity and Development

Contains fulltext : 80701.pdf (publisher's version ) (Open Access)BACKGROUND: Mammalian ATAD3 is a mitochondrial protein, which is thought to play an important role in nucleoid organization. However, its exact function is still unresolved. RESULTS: Here, we characterize the Caenorhabditis elegans (C. elegans) ATAD3 homologue (ATAD-3) and investigate its importance for mitochondrial function and development. We show that ATAD-3 is highly conserved among different species and RNA mediated interference against atad-3 causes severe defects, characterized by early larval arrest, gonadal dysfunction and embryonic lethality. Investigation of mitochondrial physiology revealed a disturbance in organellar structure while biogenesis and function, as indicated by complex I and citrate synthase activities, appeared to be unaltered according to the developmental stage. Nevertheless, we observed very low complex I and citrate synthase activities in L1 larvae populations in comparison to higher larval and adult stages. Our findings indicate that atad-3(RNAi) animals arrest at developmental stages with low mitochondrial activity. In addition, a reduced intestinal fat storage and low lysosomal content after depletion of ATAD-3 suggests a central role of this protein for metabolic activity. CONCLUSIONS: In summary, our data clearly indicate that ATAD-3 is essential for C. elegans development in vivo. Moreover, our results suggest that the protein is important for the upregulation of mitochondrial activity during the transition to higher larval stages

International travel-related control measures to contain the COVID-19 pandemic: a rapid review

BACKGROUND: In late 2019, the first cases of coronavirus disease 2019 (COVID‐19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers. OBJECTIVES: To assess the effectiveness of international travel‐related control measures during the COVID‐19 pandemic on infectious disease transmission and screening‐related outcomes. SEARCH METHODS: We searched MEDLINE, Embase and COVID‐19‐specific databases, including the Cochrane COVID‐19 Study Register and the WHO Global Database on COVID‐19 Research to 13 November 2020. SELECTION CRITERIA: We considered experimental, quasi‐experimental, observational and modelling studies assessing the effects of travel‐related control measures affecting human travel across international borders during the COVID‐19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID‐19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool for observational studies concerned with screening, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements. MAIN RESULTS: Overall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission. Most studies compared travel‐related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects. Below we outline the results for each intervention category by illustrating the findings from selected outcomes. Travel restrictions reducing or stopping cross‐border travel (31 modelling studies) The studies assessed cases avoided and shift in epidemic development. We found very low‐certainty evidence for a reduction in COVID‐19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect. There was very low‐certainty evidence that cross‐border travel controls can slow the spread of COVID‐19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure. Screening at borders (13 modelling studies; 13 observational studies) Screening measures covered symptom/exposure‐based screening or test‐based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely. For symptom/exposure‐based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate‐certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low‐certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low‐certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low‐certainty evidence), although all but one study observed this proportion to be less than 54%. For test‐based screening, one modelling study provided very low‐certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low‐certainty evidence). Quarantine (12 modelling studies) The studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low‐ to low‐certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low‐certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance. Quarantine and screening at borders (7 modelling studies; 4 observational studies) The studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low‐ to low‐certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low‐certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine. AUTHORS' CONCLUSIONS: With much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross‐border travel and quarantine of travellers, there is a lack of 'real‐world' evidence. The certainty of the evidence for most travel‐related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure‐based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure‐based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel‐related control measures from a societal perspective

C. elegans VANG-1 Modulates Life Span via Insulin/IGF-1-Like Signaling

The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans