A species-wide inventory of NLR genes and alleles in Arabidopsis thaliana

Infectious disease is both a major force of selection in nature and a prime cause of yield loss in agriculture. In plants, disease resistance is often conferred by nucleotide-binding leucine-rich repeat (NLR) proteins, intracellular immune receptors that recognize pathogen proteins and their effects on the host. Consistent with extensive balancing and positive selection, NLRs are encoded by one of the most variable gene families in plants, but the true extent of intraspecific NLR diversity has been unclear. Here, we define a nearly complete species-wide pan-NLRome in Arabidopsis thaliana based on sequence enrichment and long-read sequencing. The pan-NLRome largely saturates with approximately 40 well-chosen wild strains, with half of the pan-NLRome being present in most accessions. We chart NLR architectural diversity, identify new architectures, and quantify selective forces that act on specific NLRs and NLR domains. Our study provides a blueprint for defining pan-NLRomes

Perception of Light in Museum Environments: Comparison between Real-Life and Virtual Visual Experiences

Alternative environments to real-life have been in recent demand in regard to lighting design and in museums. In this study, the effectiveness of the perception of the museum space in simulations or virtual-based environments is studied. Answers to a questionnaire regarding lighting in four different visual experiences are compared: Real-life, virtual-video-based, virtual-photo-based and virtual-render-based. A total of 117 participants were divided into four visual experience groups. Each group answered the same lighting related questions for four exhibition halls in the Natural History Museum of the University of Pisa (Italy), which is housed in the Monumental Charterhouse of Calci. The answers were analyzed using ANOVA and a T-test. The results show that virtual experiences can be acceptable alternatives to real-life experience as the answers were indifferent in more than half of the criteria, and no criterion was affected significantly by experience, regardless of the hall’s characteristics. However, it was found that the hall’s characteristics also had an impact on the perception of the criteria in different experiences. Controlled artificial lighting or uniformly distributed lighting (full day or artificial light) were found to be more indifferent to the experience

Modulation of functional pendant chains within poly(ethylene glycol) hydrogels for refined control of protein release

Hydrogels are highly attractive delivery vehicles for therapeutic proteins. Their innate biocompatibility, hydrophilicity and aqueous permeability allow stable encapsulation and release of proteins. The release rates also can be controlled simply by altering the crosslinking density of the polymeric network. However, the crosslinking density also influences the mechanical properties of hydrogels, generally opposite to the permeability. In addition, the release of larger proteins may be hindered below critically diminished porosity determined by the crosslinking density. Herein, the physical properties of the hydrogels are tuned by presenting functional pendant chains, independent of crosslinking density. Heterobifunctional poly(ethylene glycol) monomethacrylate (PEGMA) with various end functional groups is synthesized and copolymerized with PEG dimethacrylate (PEGDA) to engineer PEG hydrogels with pendant PEG chains. The pendant chains of the PEG hydrogels consisting of sulfonate, trimethylammonium chloride, and phenyl groups are utilized to provide negative charge, positive charge and hydrophobicity, respectively, to the hydrogels. The release rates of proteins with different isoelectric points are controlled in a wide range by the type and the density of functional pendant chains via electrostatic and hydrophobic interactions

Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans

The small ciliary G protein Arl13b is required for cilium biogenesis and sonic hedgehog signaling and is mutated in patients with Joubert syndrome (JS). In this study, using Caenorhabditis elegans and mammalian cell culture systems, we investigated the poorly understood ciliary and molecular basis of Arl13b function. First, we show that Arl13b/ARL-13 localization is frequently restricted to a proximal ciliary compartment, where it associates with ciliary membranes via palmitoylation modification motifs. Next, we find that loss-of-function C. elegans arl-13 mutants possess defects in cilium morphology and ultrastructure, as well as defects in ciliary protein localization and transport; ciliary transmembrane proteins abnormally accumulate, PKD-2 ciliary abundance is elevated, and anterograde intraflagellar transport (IFT) is destabilized. Finally, we show that arl-13 interacts genetically with other ciliogenic and ciliary transport-associated genes in maintaining cilium structure/morphology and anterograde IFT stability. Together, these data implicate a role for JS-associated Arl13b at ciliary membranes, where it regulates ciliary transmembrane protein localizations and anterograde IFT assembly stability

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Islamic Monetary Economics: Insights from the Literature

This chapter reviews critical early literature of Islamic monetary economics. The prohibition of Riba has imposed challenges on Islamic economists to come up with the viable alternatives to achieve Islamic monetary policy goals. Our extensive review of theoretical and empirical literature indicates that equity based profit- and loss-sharing instruments have been proposed for conducting open market operations in an interest-free economy. Theoretically, the central bank can achieve desired goals by controlling money supply and profit-sharing ratios. The findings from empirical literature suggest that money demand tend to be more stable in an interest-free economy. Whether monetary transmission works through Islamic banking channel is controversial, but the literature is growing. These findings are not surprising as majority Muslim countries lack sustainable and equitable economic growth. Moreover, these countries suffer from higher inflation and unemployment with little or no monetary freedom due to fixed exchange rate regime, shallow financial markets and strict capital control

Source apportionment of fine particulate matter in Houston, Texas: insights to secondary organic aerosols

Online and offline measurements of ambient particulate matter (PM) near the urban and industrial Houston Ship Channel in Houston, Texas, USA, during May 2015 were utilized to characterize its chemical composition and to evaluate the relative contributions of primary, secondary, biogenic, and anthropogenic sources. Aerosol mass spectrometry (AMS) on nonrefractory PM1 (PM  ≤  1&thinsp;µm) indicated major contributions from sulfate (averaging 50&thinsp;% by mass), organic aerosol (OA, 40&thinsp;%), and ammonium (14&thinsp;%). Positive matrix factorization (PMF) of AMS data categorized OA on average as 22&thinsp;% hydrocarbon-like organic aerosol (HOA), 29&thinsp;% cooking-influenced less-oxidized oxygenated organic aerosol (CI-LO-OOA), and 48&thinsp;% more-oxidized oxygenated organic aerosol (MO-OOA), with the latter two sources indicative of secondary organic aerosol (SOA). Chemical analysis of PM2.5 (PM  ≤  2.5&thinsp;µm) filter samples agreed that organic matter (35&thinsp;%) and sulfate (21&thinsp;%) were the most abundant components. Organic speciation of PM2.5 organic carbon (OC) focused on molecular markers of primary sources and SOA tracers derived from biogenic and anthropogenic volatile organic compounds (VOCs). The sources of PM2.5 OC were estimated using molecular marker-based positive matric factorization (MM-PMF) and chemical mass balance (CMB) models. MM-PMF resolved nine factors that were identified as diesel engines (11.5&thinsp;%), gasoline engines (24.3&thinsp;%), nontailpipe vehicle emissions (11.1&thinsp;%), ship emissions (2.2&thinsp;%), cooking (1.0&thinsp;%), biomass burning (BB, 10.6&thinsp;%), isoprene SOA (11.0&thinsp;%), high-NOx anthropogenic SOA (6.6&thinsp;%), and low-NOx anthropogenic SOA (21.7&thinsp;%). Using available source profiles, CMB apportioned 41&thinsp;% of OC to primary fossil sources (gasoline engines, diesel engines, and ship emissions), 5&thinsp;% to BB, 15&thinsp;% to SOA (including 7.4&thinsp;% biogenic and 7.6&thinsp;% anthropogenic), and 39&thinsp;% to other sources that were not included in the model and are expected to be secondary.This study presents the first application of in situ AMS-PMF, MM-PMF, and CMB for OC source apportionment and the integration of these methods to evaluate the relative roles of biogenic, anthropogenic, and BB-SOA. The three source apportionment models agreed that  ∼ &thinsp;50&thinsp;% of OC is associated with primary emissions from fossil fuel use, particularly motor vehicles. Differences among the models reflect their ability to resolve sources based upon the input chemical measurements, with molecular marker-based methods providing greater source specificity and resolution for minor sources. By combining results from MM-PMF and CMB, BB was estimated to contribute 11&thinsp;% of OC, with 5&thinsp;% primary emissions and 6&thinsp;% BB-SOA. SOA was dominantly anthropogenic (28&thinsp;%) rather than biogenic (11&thinsp;%) or BB-derived. The three-model approach demonstrates significant contributions of anthropogenic SOA to fine PM. More broadly, the findings and methodologies presented herein can be used to advance local and regional understanding of anthropogenic contributions to SOA.</p

Availability, scope and quality of monkeypox clinical management guidelines globally : a systematic review

This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z) and the Bill & Melinda Gates Foundation (OPP1209135). The GloPID-R Secretariat is a project that receives funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 874667. SL is an MRC Clinical Research Training fellow (MR/T001151/1).Background Monkeypox (MPX) is an important human Orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality and inclusivity of clinical management guidelines for MPX globally. Methods For this systematic review, we searched six databases from inception until 14 October 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Results Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1–7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women and three (21%) for people living with HIV. Treatment guidance was mostly limited to advice on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression. Conclusion Our results highlight a lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A ‘living guideline’ framework is recommended. PROSPERO registration number CRD42020167361.Publisher PDFPeer reviewe

Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment

Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease

Measuring Financial Stress and Economic Sensitivity in CEE Countries

This report presents the methodology for the construction of the Financial Stress Index (FSI) and the Economic Sensitivity Index (ESI) and investigates the economic situation in twelve Central and East European Countries (CEECs) between 2001 and 2012. The objective of this paper is to capture key features of financial and economic vulnerability and examine the co-movement of economic turmoil and financial disturbances that strongly affected the CEECs in the last decade. Our main finding is that the FSI can be used as a leading indicator and can be used to recognize changing trends in the index. A shift in the value of the index proves that EU accession has a positive, but minor influence on financial stability in the CEECs. On the other hand, the impact of the introduction of the euro in Estonia, Slovakia and Slovenia is ambiguous. For most of the countries in our sample, in 2007, the FSI started to grow rapidly, reaching its peak around the third quarter of 2008. Consequently, financial stress remained high for a few quarters and started to fall gradually. For a number of countries, we observe higher financial stress in the latest period of our analysis, i.e. 2010-2012. However, the value of the FSI was significantly lower than three years earlier. The results show that indices might be helpful in predicting future recessions. However, forecasting properties seem to be limited at this stage of our work