Multidimensional mutual information methods for the analysis of covariation in multiple sequence alignments

Several methods are available for the detection of covarying positions from a multiple sequence alignment (MSA). If the MSA contains a large number of sequences, information about the proximities between residues derived from covariation maps can be sufficient to predict a protein fold. If the structure is already known, information on the covarying positions can be valuable to understand the protein mechanism. In this study we have sought to determine whether a multivariate extension of traditional mutual information (MI) can be an additional tool to study covariation. The performance of two multidimensional MI (mdMI) methods, designed to remove the effect of ternary/quaternary interdependencies, was tested with a set of 9 MSAs each containing <400 sequences, and was shown to be comparable to that of methods based on maximum entropy/pseudolikelyhood statistical models of protein sequences. However, while all the methods tested detected a similar number of covarying pairs among the residues separated by < 8 {\AA} in the reference X-ray structures, there was on average less than 65% overlap between the top scoring pairs detected by methods that are based on different principles. We have also attempted to identify whether the difference in performance among methods is due to different efficiency in removing covariation originating from chains of structural contacts. We found that the reason why methods that derive partial correlation between the columns of a MSA provide a better recognition of close contacts is not because they remove chaining effects, but because they filter out the correlation between distant residues that originates from general fitness constraints. In contrast we found that true chaining effects are expression of real physical perturbations that propagate inside proteins, and therefore are not removed by the derivation of partial correlation between variables.Comment: 21 pages, 4 figures, 1 table, supporting information containing 2 additional figures is included at the end of the manuscrip

Nutrient Use and Management Practices on United States Golf Courses

Nutrient use on United States golf courses increases management costs and has the potential to influence ecosystems. Therefore, it is critical to assess nutrient use and management practices to develop and teach best management practices. The objectives of this survey were to measure nutrient use and management practices on United States golf courses in 2021, and to determine if changes occurred since 2006. A survey was developed and distributed via e-mail to 14,033 United States golf facilities, with 1444 responding. From 2006 to 2021, the total projected nitrogen (N), available phosphorus (P2O5), and soluble potash (K2O) applied declined by 41%, 59%, and 54%, to 54,376, 13,761, and 41,386 tons, respectively. These reductions were attributed to course closures, reduced fertilized acres, reduced application rates, and nutrient use restrictions. The percentage of facilities that did not apply P2O5 increased to 21%, which is likely a result of P2O5 application restrictions. Soil testing was associated with greater application rates of N, P2O5, and K2O. Returning clippings, using precision fertilizer applications, reducing turfgrass acreage, and considering N release from soil organic matter were associated with reduced application rates of P2O5. Golf course superintendents have contributed to nationwide reductions in N, P2O5, and K2O, as evidenced by the reduction in fertilized acres and the reduction in nutrient use rates from 2006 to 2021

Survey of Pest Management Practices on US Golf Courses

Integrated pest management (IPM) is an important component of golf course maintenance and includes conventional chemical pesticide use as well as nonchemical cultural management practices. Determining how frequent pest management practices are used on golf courses is critical when developing educational and outreach programs. The objective of this study was to determine the frequency of pest management practices and pesticide mixing and storage facilities on US golf courses. A survey was sent to 14,033 operational US golf facilities with 10% responding. Reliance on all conventional chemical pesticides increased from 2015 to 2021. The reliance on biological control products declined to 14% and reliance on the nonpesticide practice of using plant growth regulators remained equivalent to 2015. The most common pest management practices included monitoring weather patterns and scouting for pests, with 93% of golf facilities reporting the use of both. The use of written IPM and pesticide application plans increased from 44% to 63% of golf facilities between 2015 and 2021, respectively. Generally, mixing and storage facilities remained unchanged from 2015 to 2021. US golf facilities continue to use nonchemical pest management practices, but reliance on chemical pesticides has increased

Experimental warming differentially affects vegetative and reproductive phenology of tundra plants

Rapid climate warming is altering Arctic and alpine tundra ecosystem structure and function, including shifts in plant phenology. While the advancement of green up and flowering are well-documented, it remains unclear whether all phenophases, particularly those later in the season, will shift in unison or respond divergently to warming. Here, we present the largest synthesis to our knowledge of experimental warming effects on tundra plant phenology from the International Tundra Experiment. We examine the effect of warming on a suite of season-wide plant phenophases. Results challenge the expectation that all phenophases will advance in unison to warming. Instead, we find that experimental warming caused: (1) larger phenological shifts in reproductive versus vegetative phenophases and (2) advanced reproductive phenophases and green up but delayed leaf senescence which translated to a lengthening of the growing season by approximately 3%. Patterns were consistent across sites, plant species and over time. The advancement of reproductive seasons and lengthening of growing seasons may have significant consequences for trophic interactions and ecosystem function across the tundra

Injury epidemiology in professional ballet: a five-season prospective study of 1596 medical attention injuries and 543 time-loss injuries

OBJECTIVES: To describe the incidence rate, severity, burden and aetiology of medical attention and time-loss injuries across five consecutive seasons at a professional ballet company. METHODS: Medical attention injuries, time-loss injuries and dance exposure hours of 123 professional ballet dancers (women: n=66, age: 28.0+/-8.3 years; men: n=57, age: 27.9+/-8.5 years) were prospectively recorded between the 2015/2016 and 2019/2020 seasons. RESULTS: The incidence rate (per 1000 hours) of medical attention injury was 3.9 (95% CI 3.3 to 4.4) for women and 3.1 (95% CI 2.6 to 3.5) for men. The incidence rate (per 1000 hours) of time-loss injury was 1.2 (95% CI 1.0 to 1.5) for women and 1.1 (95% CI 0.9 to 1.3) for men. First Soloists and Principals experienced between 2.0-2.2 additional medical attention injuries per 1000 hours and 0.9-1.1 additional time-loss injuries per 1000 hours compared with Apprentices (p</=0.025). Further, intraseason differences were observed in medical attention, but not time-loss, injury incidence rates with the highest incidence rates in early (August and September) and late (June) season months. Thirty-five per cent of time-loss injuries resulted in over 28 days of modified dance training. A greater percentage of time-loss injuries were classified as overuse (women: 50%; men: 51%) compared with traumatic (women: 40%; men: 41%). CONCLUSION: This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Constraining the fluid history of a CO2 -H2 S reservoir: insights from stable isotopes, REE and fluid inclusion microthermometry

Reservoirs that host CO2‐H2S‐bearing gases provide a key insight into crustal redox reactions such as thermochemical sulfate reduction (TSR). Despite this, there remains a poor understanding of the extent, duration, and the factors limiting this process on a reservoir scale. Here we show how a combination of petrography, fluid inclusion, rare earth element (REE), and carbon (δ13C), oxygen (δ18O), and sulfur (δ34S) stable isotope data can disentangle the fluid history of the world's largest CO2 accumulation, the LaBarge Field in Wyoming, USA. The carbonate‐hosted LaBarge Field was charged with oil around 80 Ma ago, which together with nodular anhydrite represent the reactants for TSR. The nodules exhibit two distinct trends of evolution in δ13C with both δ34S and δ18O that may be coupled to two different processes. The first trend was interpreted to reflect the coupled dissolution of anhydrite and reduction to elemental sulfur and the oxidation of organic compounds and associated precipitation of calcite during TSR. In contrast, the second trend was interpreted to be the result of the hydrothermal CO2 influx after the cessation of TSR. In addition, mass balance calculations were performed to estimate an approximate TSR reaction duration of 80 ka and to identify the availability of organic compounds as the limiting factor of the TSR process. Such an approach provides a tool for the prediction of TSR occurrence elsewhere and advancing our understanding of crustal fluid interactions

Exploring Variation and Predictors of Residential Fine Particulate Matter Infiltration

Although individuals spend the majority of their time indoors, most epidemiological studies estimate personal air pollution exposures based on outdoor levels. This almost certainly results in exposure misclassification as pollutant infiltration varies between homes. However, it is often not possible to collect detailed measures of infiltration for individual homes in large-scale epidemiological studies and thus there is currently a need to develop models that can be used to predict these values. To address this need, we examined infiltration of fine particulate matter (PM2.5) and identified determinants of infiltration for 46 residential homes in Toronto, Canada. Infiltration was estimated using the indoor/outdoor sulphur ratio and information on hypothesized predictors of infiltration were collected using questionnaires and publicly available databases. Multiple linear regression was used to develop the models. Mean infiltration was 0.52 ± 0.21 with no significant difference across heating and non-heating seasons. Predictors of infiltration were air exchange, presence of central air conditioning, and forced air heating. These variables accounted for 38% of the variability in infiltration. Without air exchange, the model accounted for 26% of the variability. Effective modelling of infiltration in individual homes remains difficult, although key variables such as use of central air conditioning show potential as an easily attainable indicator of infiltration

‘NOT A RELIGIOUS STATE’ A study of three Indonesian religious leaders on the relation of state and religion

This article explores the concept of a ‘secular state’ offered by three Indonesian religious leaders: a Catholic priest, Nicolaus Driyarkara (1913–1967), and two Muslim intellectuals who were also state officials, Mukti Ali (1923–2004) and Munawir Sjadzali (1925–2004). All three, who represented the immediate generation after the revolution for Indonesian independence from the Dutch (1945), defended the legitimacy of a secular state for Indonesia based on the state ideology Pancasila (Five Principles of Indonesia). In doing so, they argued that a religious state, for example an Islamic state, is incompatible with a plural nation that has diverse cultures, faiths, and ethnicities. The three also argued that the state should remain neutral about its citizens’ faith and should not be dominated by a single religion, i.e. Islam. Instead, the state is obliged to protect all religions embraced by Indonesians. This argument becomes a vital foundation in the establishment of Indonesia’s trajectory of unique ‘secularisation’. Whilst these three intellectuals opposed the idea of establishing a religious or Islamic state in Indonesia, it was not because they envisioned the decline of the role of religion in politics and the public domain but rather that they regarded religiosity in Indonesia as vital in nation building within a multi-religious society. In particular, the two Muslim leaders used religious legitimacy to sustain the New Order’s political stability, and harnessed state authority to modernise the Indonesian Islamic community