Evaluating perioperative stresses in children by noninvasive modalities using salivary cortisol and autonomic reactivity.

PURPOSE: Salivary cortisol (SalC) and low to high pulse ratio (LHR) were used for evaluating perioperative stresses in children. METHODS: Children aged 6 months-16 years having elective general (thoracic/abdominal) or minor (open/minimally invasive: MI) procedures underwent pulse monitoring during AM (08:00-12:00) and PM (17:00-21:00) saliva collections from the day before surgery (S-1) to 3 days after surgery (S + 3). SalC/LHR were correlated with age, sex, caregiver attendance, operative time, and surgical site/approach using mixed model analysis and face/numeric pain rating scales (FRS/NRS). RESULTS: Mean ages (years): minor-open (n = 31) 4.7 ± 2.0, thoracic-open (n = 2) 8.7 ± 4.9, thoracic-MI (n = 6) 9.6 ± 6.1, abdominal-open (n = 14) 4.3 ± 4.1, and abdominal-MI (n = 32) 8.0 ± 5.0. Postoperative SalC increased rapidly and decreased to preoperative levels by S + 3 (p < 0.001). LHR increased slightly without decreasing (p = 0.038). SalC correlated positively with operative time (p = 0.036) and open surgery (p = 0.0057), and negatively with age (p < 0.0001) and caregiver attendance (p < 0.001). SalC correlated positively with FRS (n = 51) at S + 2(PM) (p = 0.023), S + 3(AM) (p < 0.001), S + 3(PM) (p = 0.012) and NRS (n = 34) at S + 1(AM) (p = 0.031), S + 3(AM) (p < 0.044). LHR positively correlated with age (p = 0.0072), female sex (p = 0.0047), and caregiver attendance (p = 0.0026). Postoperative SalC after robotic-assisted MI was significantly lower than after open surgery at S + 2(AM) (p = 0.020). CONCLUSIONS: SalC correlated with pain. Caregiver attendance effectively alleviated stress.

Association mapping in multiple yam species (Dioscorea spp.) of quantitative trait loci for yield-related traits.

BACKGROUND: Yam (Dioscorea spp.) is multiple species with various ploidy level and considered as cash crop in many producing areas. Selection based phenotyping for yield and its related traits such as mosaic virus and anthracnose diseases resistance and plant vigor in multiple species of yam is lengthy however, marker information has proven to enhance selection efficiency. METHODOLOGY: In this study, a panel of 182 yam accessions distributed across six yam species were assessed for diversity and marker-traits association study using SNP markers generated from Diversity Array Technology platform. For the traits association analysis, the relation matrix alongside the population structure were used as co-factor to avoid false discovery using Multiple random Mixed Linear Model (MrMLM) followed by gene annotation. RESULTS: Accessions performance were significantly different (p < 0.001) across all the traits with high broad-sense heritability (H2). Phenotypic and genotypic correlations showed positive relationships between yield and vigor but negative for yield and yam mosaic disease severity. Population structure revealed k = 6 as optimal clusters-based species. A total of 22 SNP markers were identified to be associated with yield, vigor, mosaic and anthracnose diseases resistance. Gene annotation for the significant SNP loci identified some putative genes associated with primary metabolism, pest and resistance to anthracnose disease, maintenance of NADPH in biosynthetic reaction especially those involving nitro-oxidative stress for resistance to mosaic virus, and seed development, photosynthesis, nutrition use efficiency, stress tolerance, vegetative and reproductive development for tuber yield. CONCLUSION: This study provides valuable insights into the genetic control of plant vigor, anthracnose, mosaic virus resistance, and tuber yield in yam and thus, opens an avenue for developing additional genomic resources for markers-assisted selection focusing on multiple yam species.

Identification of genomic regions governing moisture and heat stress tolerance employing association mapping in rice (Oryza sativa L.).

BACKGROUND: Rice crop is damaged extremely by abiotic stress world-wide. The best approach to enhance drought tolerance in rice varieties is to identify and introgress yield QTLs with major effects. The Association mapping approach helps in the identification of genomic regions governing physiological, yield and yield attributes under moisture and heat stress conditions in diverse collections of crop germplasm, based on historic recombination events and linkage disequilibrium across the genome. METHODS AND RESULTS: The association mapping panel of 110 rice germplasm lines exhibited significant variation for all the traits in both irrigated and moisture stress conditions. The extent of yield reduction ranged to 83% during rabi, 2018-19, 53% in rabi, 2019-20 and 68% in pooled analysis. The genotypes Badami, Badshabhog, Pankaj, Varalu, Vasundhara, Vivekdhan, Krishna and Minghui63 exhibited drought tolerance with least yield penalty under moisture stress conditions. The genotypes Konark, MTU3626, NLR33671, PR118 and Triguna exhibited minimal reduction in heat stress tolerance traits. Association mapping of germplasm using 37808 SNP markers detected a total of 10 major MTA (Marker-trait association) clusters distributed on chromosomes 1, 3, 4 and 11 through mixed linear model (MLM) governing multiple traits from individual data analysis which are consistent across the years and situations. The pooled data generated a total of five MTA clusters located on chromosome 6. In addition, several novel unique MTAs were also identified. Heat stress analysis generated a total of 23 MTAs distributed on chromosomes 1, 5, 6 and 11. Candidate gene analysis detected a total of 53 and 38 genes under individual and pooled data analysis for various yield and yield attributes under control and moisture stress conditions, respectively and a total of 11 candidate genes in heat stress Conditions. CONCLUSION: The major and novel MTAs identified in the present investigation for various drought and heat tolerant traits can be utilized for breeding climate-resilient rice varieties. The candidate genes predicted for key MTAs are of great value to deploy into the rice breeding after functional characterization.

Genetic Variation, DIMBOA Accumulation, and Candidate Gene Identification in Maize Multiple Insect-Resistance.

Maize seedlings contain high amounts of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and the effect of DIMBOA is directly associated with multiple insect-resistance against insect pests such as Asian corn borer and corn leaf aphids. Although numerous genetic loci for multiple insect-resistant traits have been identified, little is known about genetic controls regarding DIMBOA content. In this study, the best linear unbiased prediction (BLUP) values of DIMBOA content in two ecological environments across 310 maize inbred lines were calculated; and their phenotypic data and BLUP values were used for marker-trait association analysis. We identified nine SSRs that were significantly associated with DIMBOA content, which explained 4.30-20.04% of the phenotypic variation. Combined with 47 original genetic loci from previous studies, we detected 19 hot loci and approximately 11 hot loci (in Bin 1.04, Bin 2.00-2.01, Bin 2.03-2.04, Bin 4.00-4.03, Bin 5.03, Bin 5.05-5.07, Bin 8.01-8.03, Bin 8.04-8.05, Bin 8.06, Bin 9.01, and Bin 10.04 regions) supported pleiotropy for their association with two or more insect-resistant traits. Within the 19 hot loci, we identified 49 candidate genes, including 12 controlling DIMBOA biosynthesis, 6 involved in sugar metabolism/homeostasis, 2 regulating peroxidases activity, 21 associated with growth and development [(auxin-upregulated RNAs (SAUR) family member and v-myb avian myeloblastosis viral oncogene homolog (MYB)], and 7 involved in several key enzyme activities (lipoxygenase, cysteine protease, restriction endonuclease, and ubiquitin-conjugating enzyme). The synergy and antagonism interactions among these genes formed the complex defense mechanisms induced by multiple insect pests. Moreover, sufficient genetic variation was reported for DIMBOA performance and SSR markers in the 310 tested maize inbred lines, and 3 highly (DIMBOA content was 402.74-528.88 µg g-1 FW) and 15 moderate (DIMBOA content was 312.92-426.56 µg g-1 FW) insect-resistant genotypes were major enriched in the Reid group. These insect-resistant inbred lines can be used as parents in maize breeding programs to develop new varieties.

cgSSR marker-based genome-wide association study identified genomic regions for panicle characters and yield in rice (Oryza sativa L.).

BACKGROUND: To improve production efficiency, positive alleles corresponding to yield-related attributes must be accumulated in a single elite background. We designed and used cgSSR markers, which are superior to random SSR markers in genome-wide association study, to identify genomic regions that contribute to panicle characters and grain yield in this study. RESULTS: As evidenced by the high polymorphic information content value and gene diversity coefficient, the new cgSSR markers were determined to be highly informative. These cgSSR markers were employed to generate genotype data for an association panel evaluated for four panicle characters and grain yield over three seasons. For five traits, 17 significant marker-trait associations on six chromosomes were discovered. The percentage of phenotypic variance that could be explained ranged from 4% to 13%. Unrelated gene-derived markers had a strong association with target traits as well. CONCLUSION: Trait-associated cgSSR markers derived from corresponding or related genes ensure their utility in direct allele selection, while other linked markers aid in allele selection indirectly by altering the phenotype of interest. Through a marker-assisted breeding approach, these marker-trait associations can be leveraged to accumulate favourable alleles for yield enhancement in rice. © 2022 Society of Chemical Industry.

An extended health belief model for COVID-19: understanding the media-based processes leading to social distancing and panic buying.

Building on the health belief model (HBM), this research tests, over six months, how the exposure to COVID-related information in the media affects fear, which in turn conditions beliefs about the severity of the virus, susceptibility of getting the virus, and benefits of safety measures. These health beliefs ultimately lead to social distancing and panic buying. As a first contribution, we find that fear is not directly triggered by the objective severity of a crisis, but rather formed over time by the way individuals are exposed to media. Second, we show that fear affects behaviors through the components of the HBM which relate to the risks/benefits of a situation. Last, we find that critical thinking about media content amplifies the "adaptive" responses of our model (e.g., health beliefs, social distancing) and reduces its "maladaptive" responses (e.g., panic buying). Interestingly, we note that the beneficial effect of critical thinking about media content disappears as the level of fear increases over time. The implications of these findings for policymakers, media companies, and theory are further discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s11747-022-00865-8.

Genome-wide association studies dissect the G × E interaction for agronomic traits in a worldwide collection of safflowers (Carthamus tinctorius L.).

Genome-wide association studies were conducted using a globally diverse safflower (Carthamus tinctorius L.) Genebank collection for grain yield (YP), days to flowering (DF), plant height (PH), 500 seed weight (SW), seed oil content (OL), and crude protein content (PR) in four environments (sites) that differed in water availability. Phenotypic variation was observed for all traits. YP exhibited low overall genetic correlations (rGoverall) across sites, while SW and OL had high rGoverall and high pairwise genetic correlations (rGij) across all pairwise sites. In total, 92 marker-trait associations (MTAs) were identified using three methods, single locus genome-wide association studies (GWAS) using a mixed linear model (MLM), the Bayesian multi-locus method (BayesR), and meta-GWAS. MTAs with large effects across all sites were detected for OL, SW, and PR, and MTAs specific for the different water stress sites were identified for all traits. Five MTAs were associated with multiple traits; 4 of 5 MTAs were variously associated with the three traits of SW, OL, and PR. This study provided insights into the phenotypic variability and genetic architecture of important safflower agronomic traits under different environments. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01295-8.

An efficient multi-locus mixed model framework for the detection of small and linked QTLs in F2.

In the genetic system that regulates complex traits, metabolites, gene expression levels, RNA editing levels and DNA methylation, a series of small and linked genes exist. To date, however, little is known about how to design an efficient framework for the detection of these kinds of genes. In this article, we propose a genome-wide composite interval mapping (GCIM) in F2. First, controlling polygenic background via selecting markers in the genome scanning of linkage analysis was replaced by estimating polygenic variance in a genome-wide association study. This can control large, middle and minor polygenic backgrounds in genome scanning. Then, additive and dominant effects for each putative quantitative trait locus (QTL) were separately scanned so that a negative logarithm P-value curve against genome position could be separately obtained for each kind of effect. In each curve, all the peaks were identified as potential QTLs. Thus, almost all the small-effect and linked QTLs are included in a multi-locus model. Finally, adaptive least absolute shrinkage and selection operator (adaptive lasso) was used to estimate all the effects in the multi-locus model, and all the nonzero effects were further identified by likelihood ratio test for true QTL identification. This method was used to reanalyze four rice traits. Among 25 known genes detected in this study, 16 small-effect genes were identified only by GCIM. To further demonstrate GCIM, a series of Monte Carlo simulation experiments was performed. As a result, GCIM is demonstrated to be more powerful than the widely used methods for the detection of closely linked and small-effect QTLs.

Genome-wide association mapping revealed syntenic loci QFhb-4AL and QFhb-5DL for Fusarium head blight resistance in common wheat (Triticum aestivum L.).

BACKGROUND: Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is a major threat to wheat production and food security worldwide. Breeding stably and durably resistant cultivars is the most effective approach for managing and controlling the disease. The success of FHB resistance breeding relies on identification of an effective resistant germplasm. We conducted a genome-wide association study (GWAS) using the high-density wheat 90 K single nucleotide polymorphism (SNP) assays to better understand the genetic basis of FHB resistance in natural population and identify associated molecular markers. RESULTS: The resistance to FHB fungal spread along the rachis (Type II resistance) was evaluated on 171 wheat cultivars in the 2016-2017 (abbr. as 2017) and 2017-2018 (abbr. as 2018) growing seasons. Using Illumina Infinum iSelect 90 K SNP genotyping data, a genome-wide association study (GWAS) identified 26 loci (88 marker-trait associations), which explained 6.65-14.18% of the phenotypic variances. The associated loci distributed across all chromosomes except 2D, 6A, 6D and 7D, with those on chromosomes 1B, 4A, 5D and 7A being detected in both years. New loci for Type II resistance were found on syntenic genomic regions of chromsome 4AL (QFhb-4AL, 621.85-622.24 Mb) and chromosome 5DL (QFhb-5DL, 546.09-547.27 Mb) which showed high collinearity in gene content and order. SNP markers wsnp_JD_c4438_5568170 and wsnp_CAP11_c209_198467 of 5D, reported previously linked to a soil-borne wheat mosaic virus (SBWMV) resistance gene, were also associated with FHB resistance in this study. CONCLUSION: The syntenic FHB resistant loci and associated SNP markers identified in this study are valuable for FHB resistance breeding via marker-assisted selection.

Phenotypic and genetic variation in phosphorus-deficiency-tolerance traits in Chinese wheat landraces.

BACKGROUND: Phosphorus deficiency is a major limiting factors for affecting crop production globally. To understand the genetic variation of phosphorus-deficiency-tolerance, a total of 15 seedling traits were evaluated among 707 Chinese wheat landraces under application of phosphorus (AP) and non-application of phosphorus (NP). A total of 18,594 single-nucleotide polymorphisms and 38,678 diversity arrays technology sequencing markers were used to detect marker-trait associations under AP and NP. RESULTS: Top ten genotypes with extremely tolerance and bottommost ten genotypes with extremely sensitivity were selected from 707 Chinese wheat landraces for future breeding and genetic analysis. A total of 55 significant markers (81 marker-trait associations) for 13 traits by both CMLM and SUPER method. These were distributed on chromosomes 1A, 1B, 2A, 2B, 2D, 3A, 4B, 5A, 5B, 6A, 6B, 6D, 7A and 7B. Considering the linkage disequilibrium decay distance, 25 and 12 quantitative trait loci (QTL) were detected under AP and NP, respectively (9 QTL were specific to NP). CONCLUSIONS: The extremely tolerant landraces could be used for breeding phosphorus-deficiency-tolerant cultivars. The QTL could be useful in wheat breeding through marker-assisted selection. Our findings provide new insight into the genetic analysis of P-deficiency-tolerance, and will be helpful for breeding P-deficiency-tolerant cultivars.

Genetic signatures of high-altitude adaptation in Tibetans.

Indigenous Tibetan people have lived on the Tibetan Plateau for millennia. There is a long-standing question about the genetic basis of high-altitude adaptation in Tibetans. We conduct a genome-wide study of 7.3 million genotyped and imputed SNPs of 3,008 Tibetans and 7,287 non-Tibetan individuals of Eastern Asian ancestry. Using this large dataset, we detect signals of high-altitude adaptation at nine genomic loci, of which seven are unique. The alleles under natural selection at two of these loci [methylenetetrahydrofolate reductase (MTHFR) and EPAS1] are strongly associated with blood-related phenotypes, such as hemoglobin, homocysteine, and folate in Tibetans. The folate-increasing allele of rs1801133 at the MTHFR locus has an increased frequency in Tibetans more than expected under a drift model, which is probably a consequence of adaptation to high UV radiation. These findings provide important insights into understanding the genomic consequences of high-altitude adaptation in Tibetans.

Semen production and semen quality of indigenous buffalo breeds under hot semiarid climatic conditions in India.

Semen data comprising of 97,023 ejaculates of 197 bulls from 6 buffalo breeds were analyzed. The traits considered were as follows: ejaculate volume, sperm concentration, mass activity, initial and post-thaw motility, total sperm, and total motile sperm before and after thawing as well as a composite trait equal to the theoretical number of doses which can be produced from each given ejaculate. The objective was to measure the semen production potential of indigenous buffalo bulls and identify factors affecting these traits. A linear mixed model was used, including a random bull effect along with other fixed factors: the order of the ejaculate on a particular day, the interval between collections, the time of collection, the breed, the age at collection, the semen collector, and the year and month of collection. The study showed breed wise variation for all traits. The first ejaculate of a bull on a particular day was superior to the second for nearly all the traits. Longer collection intervals are better than shorter intervals for all the parameters, although short collection interval of 2 to 4 days produced higher yield in terms of total semen doses without hampering semen quality. The study also showed a slight decrease of semen quality with time of collection within a day. The Murrah breed showed comparatively consistent performance during their whole life compared with the other breeds. Repeatability estimates for semen traits were found to be low (0.09 for mass activity) to relatively large (> 0.4 for volume and concentration). A negative correlation was found between bull effects for semen volume and concentration while a high positive correlation was found between mass activity, initial motility, and post-thaw motility. Results of the study will help in suggesting suitable management and breeding plans for semen production traits.

Dissection of complicate genetic architecture and breeding perspective of cottonseed traits by genome-wide association study.

BACKGROUND: Cottonseed is one of the most important raw materials for plant protein, oil and alternative biofuel for diesel engines. Understanding the complex genetic basis of cottonseed traits is requisite for achieving efficient genetic improvement of the traits. However, it is not yet clear about their genetic architecture in genomic level. GWAS has been an effective way to explore genetic basis of quantitative traits in human and many crops. This study aims to dissect genetic mechanism seven cottonseed traits by a GWAS for genetic improvement. RESULTS: A genome-wide association study (GWAS) based on a full gene model with gene effects as fixed and gene-environment interaction as random, was conducted for protein, oil and 5 fatty acids using 316 accessions and ~ 390 K SNPs. Totally, 124 significant quantitative trait SNPs (QTSs), consisting of 16, 21, 87 for protein, oil and fatty acids (palmitic, linoleic, oleic, myristic, stearic), respectively, were identified and the broad-sense heritability was estimated from 71.62 to 93.43%; no QTS-environment interaction was detected for the protein, the palmitic and the oleic contents; the protein content was predominantly controlled by epistatic effects accounting for 65.18% of the total variation, but the oil content and the fatty acids except the palmitic were mainly determined by gene main effects and no epistasis was detected for the myristic and the stearic. Prediction of superior pure line and hybrid revealed the potential of the QTSs in the improvement of cottonseed traits, and the hybrid could achieve higher or lower genetic values compared with pure lines. CONCLUSIONS: This study revealed complex genetic architecture of seven cottonseed traits at whole genome-wide by mixed linear model approach; the identified genetic variants and estimated genetic component effects of gene, gene-gene and gene-environment interaction provide cotton geneticist or breeders new knowledge on the genetic mechanism of the traits and the potential molecular breeding design strategy.

Genome-wide association study of rice grain width variation.

Seed size is variable within many plant species, and understanding the underlying genetic factors can provide insights into mechanisms of local environmental adaptation. Here we make use of the abundant genomic and germplasm resources available for rice (Oryza sativa) to perform a large-scale genome-wide association study (GWAS) of grain width. Grain width varies widely within the crop and is also known to show climate-associated variation across populations of its wild progenitor. Using a filtered dataset of >1.9 million genome-wide SNPs in a sample of 570 cultivated and wild rice accessions, we performed GWAS with two complementary models, GLM and MLM. The models yielded 10 and 33 significant associations, respectively, and jointly yielded seven candidate locus regions, two of which have been previously identified. Analyses of nucleotide diversity and haplotype distributions at these loci revealed signatures of selection and patterns consistent with adaptive introgression of grain width alleles across rice variety groups. The results provide a 50% increase in the total number of rice grain width loci mapped to date and support a polygenic model whereby grain width is shaped by gene-by-environment interactions. These loci can potentially serve as candidates for studies of adaptive seed size variation in wild grass species.

Effect of 48-week pegylated interferon α-2a or nucleos(t)ide analogue therapy on renal function in Chinese patients with chronic hepatitis B.

BACKGROUND: Controversy remains as to whether antiviral agents contribute to renal dysfunction in patients with chronic hepatitis B virus (HBV) infection. Thus, the aim of study was to analyze the changes in renal function of chronic hepatitis B (CHB) patients in response to anti-HBV therapy and the association with treatments. METHOD: We performed a retrospective observational cohort study to investigate factors associated with renal function in 249 Chinese CHB patients who were treated with pegylated interferon α-2a (PEG-IFN-α-2a) or nucleos(t)ide analogues for 48 weeks. Changes of estimated glomerular filtration rate (eGFR), which was computed with both the Chronic Kidney Disease Epidemiology Collaboration and the Modification of Diet in Renal Disease formulas, were tested by repeated measures One-way analysis of variance within groups. A linear mixed effects model for repeated measures was also used to evaluate the association between baseline information and eGFR changes over time in all enrolled patients. The model considered the baseline age, sex, HBV DNA, aminotransferase, blood urea nitrogen, treatment group, time, and group-by-time interaction as fixed effects and incorporated random effects for individual subjects. RESULTS: The eGFR increased in patients given PEG-IFN-α-2a, decreased in patients given adefovir, but remained stable in patients given entecavir. Age and blood urea nitrogen were significant negative predictive factors for eGFR changes. CONCLUSION: In real-life study, PEG-IFN-α-2a therapy in CHB patients increased eGFR, thus may associate with renoprotective effects when compared with adefovir or entecavir therapies.

Power of family-based association designs to detect rare variants in large pedigrees using imputed genotypes.

Recently, the "Common Disease-Multiple Rare Variants" hypothesis has received much attention, especially with current availability of next-generation sequencing. Family-based designs are well suited for discovery of rare variants, with large and carefully selected pedigrees enriching for multiple copies of such variants. However, sequencing a large number of samples is still prohibitive. Here, we evaluate a cost-effective strategy (pseudosequencing) to detect association with rare variants in large pedigrees. This strategy consists of sequencing a small subset of subjects, genotyping the remaining sampled subjects on a set of sparse markers, and imputing the untyped markers in the remaining subjects conditional on the sequenced subjects and pedigree information. We used a recent pedigree imputation method (GIGI), which is able to efficiently handle large pedigrees and accurately impute rare variants. We used burden and kernel association tests, famWS and famSKAT, which both account for family relationships and heterogeneity of allelic effect for famSKAT only. We simulated pedigree sequence data and compared the power of association tests for pseudosequence data, a subset of sequence data used for imputation, and all subjects sequenced. We also compared, within the pseudosequence data, the power of association test using best-guess genotypes and allelic dosages. Our results show that the pseudosequencing strategy considerably improves the power to detect association with rare variants. They also show that the use of allelic dosages results in much higher power than use of best-guess genotypes in these family-based data. Moreover, famSKAT shows greater power than famWS in most of scenarios we considered.

Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees.

In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant identification. Because of the high cost of sequencing technologies, imputation methods are important for increasing the amount of information at low cost. A recent family-based imputation method, Genotype Imputation Given Inheritance (GIGI), is able to handle large pedigrees and accurately impute rare variants, but does less well for common variants where population-based methods perform better. Here, we propose a flexible approach to combine imputation data from both family- and population-based methods. We also extend the Sequence Kernel Association Test for Rare and Common variants (SKAT-RC), originally proposed for data from unrelated subjects, to family data in order to make use of such imputed data. We call this extension "famSKAT-RC." We compare the performance of famSKAT-RC and several other existing burden and kernel association tests. In simulated pedigree sequence data, our results show an increase of imputation accuracy from use of our combining approach. Also, they show an increase of power of the association tests with this approach over the use of either family- or population-based imputation methods alone, in the context of rare and common variants. Moreover, our results show better performance of famSKAT-RC compared to the other considered tests, in most scenarios investigated here.

Effect of nucleoside and nucleotide analogues on renal function in patients with chronic hepatitis B virus monoinfection.

BACKGROUND & AIMS: There is controversy regarding whether nucleos(t)ide analogues contribute to renal impairment in patients with chronic hepatitis B virus (HBV) infection. We analyzed changes in renal function in patients with chronic HBV infection and whether these were associated with treatment or comorbidities. METHODS: We performed a longitudinal observational study to investigate factors associated with renal function in 214 patients (median age, 43 y; 69.2% men) with compensated chronic HBV monoinfection treated with 343 lines of nucleos(t)ide analogues (210 monotherapies, 133 combinations) between 1990 and 2012 (median time, 2.4 y) in France. A linear mixed-effect model was used to model variations of estimated glomerular filtration rate (eGFR, computed with the Chronic Kidney Disease Epidemiology Collaboration formula), adjusting for age, sex, geographic origin, initial liver fibrosis, level of HBV DNA, and an eGFR less than 90 mL/min/1.73 m(2). RESULTS: The eGFR decreased in patients given adefovir dipivoxil as monotherapy or in a combination (P < .0001 and P < .002, respectively), and remained stable in patients given lamivudine, tenofovir disoproxil fumarate, or entecavir. The eGFR decreased in patients with a baseline eGFR of less than 90 mL/min/1.73 m2, regardless of treatment. The eGFR remained stable or increased, regardless of treatment, in patients with a baseline eGFR of 90 mL/min/1.73 m2 or greater and with an initial HBV DNA level of 100,000 IU/mL or greater. Patients born in areas of high endemicity of HBV were more prone to increases in eGFR with treatment. CONCLUSIONS: In a real-life study, the eGFR remained stable or increased over time in patients with chronic HBV monoinfection with a baseline eGFR of 90 mL/min/1.73 m2 or higher and treated with tenofovir disoproxil fumarate or entecavir. Patients born in an area of high endemicity of HBV who had initial levels of HBV DNA of 100,000 IU/mL or greater were more likely to have increased eGFR with treatment.

Genome-wide association of drought-related and biomass traits with HapMap SNPs in Medicago truncatula.

Improving drought tolerance of crop plants is a major goal of plant breeders. In this study, we characterized biomass and drought-related traits of 220 Medicago truncatula HapMap accessions. Characterized traits included shoot biomass, maximum leaf size, specific leaf weight, stomatal density, trichome density and shoot carbon-13 isotope discrimination (δ(13) C) of well-watered M. truncatula plants, and leaf performance in vitro under dehydration stress. Genome-wide association analyses were carried out using the general linear model (GLM), the standard mixed linear model (MLM) and compressed MLM (CMLM) in TASSEL, which revealed significant overestimation of P-values by CMLM. For each trait, candidate genes and chromosome regions containing SNP markers were found that are in significant association with the trait. For plant biomass, a 0.5 Mbp region on chromosome 2 harbouring a plasma membrane intrinsic protein, PIP2, was discovered that could potentially be targeted to increase dry matter yield. A protein disulfide isomerase-like protein was found to be tightly associated with both shoot biomass and leaf size. A glutamate-cysteine ligase and an aldehyde dehydrogenase family protein with Arabidopsis homologs strongly expressed in the guard cells were two of the top genes identified by stomata density genome-wide association studies analysis.

Modeling the effects of temperature and pH on the resistance of Alicyclobacillus acidoterrestris in conventional heat-treated fruit beverages through a meta-analysis approach.

In this work, all publicly-accessible published findings on Alicyclobacillus acidoterrestris heat resistance in fruit beverages as affected by temperature and pH were compiled. Then, study characteristics (protocols, fruit and variety, °Brix, pH, temperature, heating medium, culture medium, inactivation method, strains, etc.) were extracted from the primary studies, and some of them incorporated to a meta-analysis mixed-effects linear model based on the basic Bigelow equation describing the heat resistance parameters of this bacterium. The model estimated mean D* values (time needed for one log reduction at a temperature of 95 °C and a pH of 3.5) of Alicyclobacillus in beverages of different fruits, two different concentration types, with and without bacteriocins, and with and without clarification. The zT (temperature change needed to cause one log reduction in D-values) estimated by the meta-analysis model were compared to those ('observed' zT values) reported in the primary studies, and in all cases they were within the confidence intervals of the model. The model was capable of predicting the heat resistance parameters of Alicyclobacillus in fruit beverages beyond the types available in the meta-analytical data. It is expected that the compilation of the thermal resistance of Alicyclobacillus in fruit beverages, carried out in this study, will be of utility to food quality managers in the determination or validation of the lethality of their current heat treatment processes.