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High nighttime temperature (HNT) is a major obstacle in rice production worldwide. It severely impacts spikelet fertility and induces grain chalk, the two undesirable factors leading to yield and quality decline in rice. Recently, major efforts have been undertaken to understand the genetic mechanisms underlying HNT tolerance. Here, we highlight phenotypic diversity and recent studies on breeding, genomics, and gene editing targeting this trait. These studies point to the challenges in the process as HNT tolerance has so far been found only in non-adapted varieties, and no known modern cultivar bred in the United States is able to withstand exposure to HNT during the reproductive stage. At the same time, identification of the tolerant genotypes enabled genomics, opened up tortuous but promising approaches for breeding, and showed a path for gene editing towards HNT tolerance. The recent advances have set a strong foundation for addressing this current and looming threat., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal relations that could influence the work discussed in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Key Message: Incorporating feature-engineered environmental data into machine learning-based genomic prediction models is an efficient approach to indirectly model genotype-by-environment interactions. Complementing phenotypic traits and molecular markers with high-dimensional data such as climate and soil information is becoming a common practice in breeding programs. This study explored new ways to combine non-genetic information in genomic prediction models using machine learning. Using the multi-environment trial data from the Genomes To Fields initiative, different models to predict maize grain yield were adjusted using various inputs: genetic, environmental, or a combination of both, either in an additive (genetic-and-environmental; G+E) or a multiplicative (genotype-by-environment interaction; GEI) manner. When including environmental data, the mean prediction accuracy of machine learning genomic prediction models increased up to 7% over the well-established Factor Analytic Multiplicative Mixed Model among the three cross-validation scenarios evaluated. Moreover, using the G+E model was more advantageous than the GEI model given the superior, or at least comparable, prediction accuracy, the lower usage of computational memory and time, and the flexibility of accounting for interactions by construction. Our results illustrate the flexibility provided by the ML framework, particularly with feature engineering. We show that the feature engineering stage offers a viable option for envirotyping and generates valuable information for machine learning-based genomic prediction models. Furthermore, we verified that the genotype-by-environment interactions may be considered using tree-based approaches without explicitly including interactions in the model. These findings support the growing interest in merging high-dimensional genotypic and environmental data into predictive modeling., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Norovirus is a major cause of acute diarrheal disease (ADD) outbreaks worldwide. In the present study, we investigated an ADD outbreak caused by norovirus in several municipalities of Santa Catarina state during the summer season, southern Brazil in 2023. As of the 10th epidemiological week of 2023, approximately 87 000 ADD cases were reported, with the capital, Florianópolis, recording the highest number of cases throughout the weeks. By using RT-qPCR and sequencing, we detected 10 different genotypes, from both genogroups (G) I and II. Some rare genotypes were also identified. Additionally, rotavirus and human adenovirus were sporadically detected among the ADD cases. Several features of the outbreak suggest that sewage-contaminated water could played a role in the surge of ADD cases. Storm events in Santa Catarina state that preceded the outbreak likely increased the discharge of contaminated wastewater and stormwater into water bodies, such as rivers and beaches during a high touristic season in the state. Climate change-induced extreme weather events, including intensified rainfall and frequent floods, can disturb healthcare and sanitation systems. Implementing public policies for effective sanitation, particularly during peak times, is crucial to maintain environmental equilibrium and counter marine pollution., (© 2023 Wiley Periodicals LLC.)

Key Message: We demonstrate potential for improved multi-environment genomic prediction accuracy using structural variant markers. However, the degree of observed improvement is highly dependent on the genetic architecture of the trait. Breeders commonly use genetic markers to predict the performance of untested individuals as a way to improve the efficiency of breeding programs. These genomic prediction models have almost exclusively used single nucleotide polymorphisms (SNPs) as their source of genetic information, even though other types of markers exist, such as structural variants (SVs). Given that SVs are associated with environmental adaptation and not all of them are in linkage disequilibrium to SNPs, SVs have the potential to bring additional information to multi-environment prediction models that are not captured by SNPs alone. Here, we evaluated different marker types (SNPs and/or SVs) on prediction accuracy across a range of genetic architectures for simulated traits across multiple environments. Our results show that SVs can improve prediction accuracy, but it is highly dependent on the genetic architecture of the trait and the relative gain in accuracy is minimal. When SVs are the only causative variant type, 70% of the time SV predictors outperform SNP predictors. However, the improvement in accuracy in these instances is only 1.5% on average. Further simulations with predictors in varying degrees of LD with causative variants of different types (e.g., SNPs, SVs, SNPs and SVs) showed that prediction accuracy increased as linkage disequilibrium between causative variants and predictors increased regardless of the marker type. This study demonstrates that knowing the genetic architecture of a trait in deciding what markers to use in large-scale genomic prediction modeling in a breeding program is more important than what types of markers to use., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the USA, DENV-2 epidemics have been dominated by DENV-2 genotype Asian-American (DENV-2-GIII), and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. The phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We hypothesize that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier against symptomatic homotypic reinfections by DENV-2-GII, leading to sustained cryptic circulation in asymptomatic cases and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understanding the potential impact of DENV-2-GII in the coming years., Competing Interests: The authors report there are no competing interests to declare., (© The Author(s) 2023. Published by Oxford University Press.)

Understanding how plants adapt to specific environmental changes and identifying genetic markers associated with phenotypic plasticity can help breeders develop plant varieties adapted to a rapidly changing climate. Here, we propose the use of marker effect networks as a novel method to identify markers associated with environmental adaptability. These marker effect networks are built by adapting commonly used software for building gene coexpression networks with marker effects across growth environments as the input data into the networks. To demonstrate the utility of these networks, we built networks from the marker effects of ∼2,000 nonredundant markers from 400 maize hybrids across 9 environments. We demonstrate that networks can be generated using this approach, and that the markers that are covarying are rarely in linkage disequilibrium, thus representing higher biological relevance. Multiple covarying marker modules associated with different weather factors throughout the growing season were identified within the marker effect networks. Finally, a factorial test of analysis parameters demonstrated that marker effect networks are relatively robust to these options, with high overlap in modules associated with the same weather factors across analysis parameters. This novel application of network analysis provides unique insights into phenotypic plasticity and specific environmental factors that modulate the genome., Competing Interests: Conflicts of interest The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The pandemic caused by COVID-19 and the emergence of new variants of SARS-CoV-2 have generated clinical and epidemiological impacts on a global scale. The use of strategies for monitoring viral circulation and identifying mutations in genomic regions involved in host interaction are important measures to mitigate viral dissemination and reduce its likely complications on population health. In this context, the objective of this work was to explore the potential of high-resolution melting (HRM) analysis combined with one-step real-time reverse transcription PCR in a closed-tube system, as a fast and convenient method of screening for SARS-CoV-2 mutations with possible implications on host-pathogen interactions. The HRM analyses allowed the distinction of the Gamma, Zeta, Alpha, Delta, and Omicron variants against the predecessors (B.1.1.28, B.1.1.33) of occurrence in Brazil. It is concluded that the molecular tool standardized here has the potential to optimize the genomic surveillance of SARS-CoV-2, and could be adapted for genomic surveillance of other pathogens, due to its ability to detect, prior to sequencing, samples suggestive of new variants, selecting them more assertively and earlier for whole genome sequencing when compared to random screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The rapid spread of the SARS-CoV-2 Variant of Concern (VOC) Gamma in Amazonas during early 2021 fueled a second large COVID-19 epidemic wave and raised concern about the potential role of reinfections. Very few cases of reinfection associated with the VOC Gamma have been reported to date, and their potential impact on clinical, immunological, and virological parameters remains largely unexplored. Here we describe 25 cases of SARS-CoV-2 reinfection in Brazil. SARS-CoV-2 genomic analysis confirmed that individuals were primo-infected with distinct viral lineages between March and December 2020 (B.1.1, B.1.1.28, B.1.1.33, B.1.195, and P.2) and reinfected with the VOC Gamma between 3 to 12 months after primo-infection. We found a similar mean cycle threshold (Ct) value and limited intra-host viral diversity in both primo-infection and reinfection samples. Sera of 14 patients tested 10-75 days after reinfection displayed detectable neutralizing antibodies (NAb) titers against SARS-CoV-2 variants that circulated before (B.1.*), during (Gamma), and after (Delta and Omicron) the second epidemic wave in Brazil. All individuals had milder or no symptoms after reinfection, and none required hospitalization. These findings demonstrate that individuals reinfected with the VOC Gamma may display relatively high RNA viral loads at the upper respiratory tract after reinfection, thus contributing to onward viral transmissions. Despite this, our study points to a low overall risk of severe Gamma reinfections, supporting that the abrupt increase in hospital admissions and deaths observed in Amazonas and other Brazilian states during the Gamma wave was mostly driven by primary infections. Our findings also indicate that most individuals analyzed developed a high anti-SARS-CoV-2 NAb response after reinfection that may provide some protection against reinfection or disease by different SARS-CoV-2 variants., (© 2023. The Author(s).)

SARS-CoV-2 genome surveillance is important for monitoring risk groups and health workers as well as data on new cases and mortality rate due to COVID-19. We characterized the circulation of SARS-CoV-2 variants from May 2021 to April 2022 in the state of Santa Catarina, southern Brazil, and evaluated the similarity between variants present in the population and healthcare workers (HCW). A total of 5291 sequenced genomes demonstrated the circulation of 55 strains and four variants of concern (Alpha, Delta, Gamma and Omicron-sublineages BA.1 and BA.2). The number of cases was relatively low in May 2021, but the number of deaths was higher with the Gamma variant. There was a significant increase in both numbers between December 2021 and February 2022, peaking in mid-January 2022, when the Omicron variant dominated. After May 2021, two distinct variant groups (Delta and Omicron) were observed, equally distributed among the five Santa Catarina mesoregions. Moreover, from November 2021 to February 2022, similar variant profiles between HCW and the general population were observed, and a quicker shift from Delta to Omicron in HCW than in the general population. This demonstrates the importance of HCW as a sentinel group for monitoring disease trends in the general population.

The influenza A virus (IAV) is of a major public health concern as it causes annual epidemics and has the potential to cause pandemics. At present, the neuraminidase inhibitors (NAIs) are the most widely used anti-influenza drugs, but, more recently, the drug baloxavir marboxil (BXM), a polymerase inhibitor, has also been licensed in some countries. Mutations in the viral genes that encode the antiviral targets can lead to treatment resistance. Worldwide, a low prevalence of antiviral resistant strains has been reported. Despite that, this situation can change rapidly, and resistant strain surveillance is a priority. Thus, the aim of this was to evaluate Brazilian IAVs antiviral resistance from 2017 to 2019 through the identification of viral mutations associated with reduced inhibition of the drugs and by testing the susceptibility of IAV isolates to oseltamivir (OST), the most widely used NAI drug in the country. Initially, we analyzed 282 influenza A(H1N1)pdm09 and 455 A(H3N2) genetic sequences available on GISAID. The amino acid substitution (AAS) NA:S247N was detected in one A(H1N1)pdm09 strain. We also identified NA:I222V ( n = 6) and NA:N329K ( n = 1) in A(H3N2) strains. In addition, we performed a molecular screening for NA:H275Y in 437 A(H1N1)pdm09 samples, by pyrosequencing, which revealed a single virus harboring this mutation. Furthermore, the determination of OST IC 50 values for 222 A(H1N1)pdm09 and 83 A(H3N2) isolates revealed that all isolates presented a normal susceptibility profile to the drug. Interestingly, we detected one A(H3N2) virus presenting with PA:E119D AAS. Moreover, the majority of the IAV sequences had the M2:S31N adamantanes resistant marker. In conclusion, we show a low prevalence of Brazilian IAV strains with NAI resistance markers, in accordance with what is reported worldwide, indicating that NAIs still remain an option for the treatment of influenza infections in Brazil. However, surveillance of influenza resistance should be strengthened in the country for improving the representativeness of investigated viruses and the robustness of the analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sousa, Martins, Miranda, Garcia, Resende, Santos, Debur, Rodrigues, Cavalcanti, Gregianini, Iani, Pereira, Fernandes, Ferreira, Santos, Motta, Brown, Almeida, Siqueira and Matos.)

Genomic loci that control the variance of agronomically important traits are increasingly important due to the profusion of unpredictable environments arising from climate change. The ability to identify such variance-controlling loci in association studies will be critical for future breeding efforts. Two statistical approaches that have already been used in the variance genome-wide association study (vGWAS) paradigm are the Brown-Forsythe test (BFT) and the double generalized linear model (DGLM). To ensure that these approaches are deployed as effectively as possible, it is critical to study the factors that influence their ability to identify variance-controlling loci. We used genome-wide marker data in maize (Zea mays L.) and Arabidopsis thaliana to simulate traits controlled by epistasis, genotype by environment (GxE) interactions, and variance quantitative trait nucleotides (vQTNs). We then quantified true and false positive detection rates of the BFT and DGLM across all simulated traits. We also conducted a vGWAS using both the BFT and DGLM on plant height in a maize diversity panel. The observed true positive detection rates at the maximum sample size considered (N = 2815) suggest that both of these vGWAS approaches are capable of identifying epistasis and GxE for sufficiently large sample sizes. We also noted that the DGLM decisively outperformed the BFT for simulated traits controlled by vQTNs at sample sizes of N = 500. Although we conclude that there are still certain aspects of vGWAS approaches that need further refinement, this study suggests that the BFT and DGLM are capable of identifying variance-controlling loci in current state-of-the-art plant or agronomic data sets., (© 2022. The Author(s), under exclusive licence to The Genetics Society.)

The ability to accurately quantify the simultaneous effect of multiple genomic loci on multiple traits is now possible due to current and emerging high-throughput genotyping and phenotyping technologies. To date, most efforts to quantify these genotype-to-phenotype relationships have focused on either multi-trait models that test a single marker at a time or multi-locus models that quantify associations with a single trait. Therefore, the purpose of this study was to compare the performance of a multi-trait, multi-locus stepwise (MSTEP) model selection procedure we developed to (a) a commonly used multi-trait single-locus model and (b) a univariate multi-locus model. We used real marker data in maize (Zea mays L.) and soybean (Glycine max L.) to simulate multiple traits controlled by various combinations of pleiotropic and nonpleiotropic quantitative trait nucleotides (QTNs). In general, we found that both multi-trait models outperformed the univariate multi-locus model, especially when analyzing a trait of low heritability. For traits controlled by either a combination of pleiotropic and nonpleiotropic QTNs or a large number of QTNs (i.e., 50), our MSTEP model often outperformed at least one of the two alternative models. When applied to the analysis of two tocochromanol-related traits in maize grain, MSTEP identified the same peak-associated marker that has been reported in a previous study. We therefore conclude that MSTEP is a useful addition to the suite of statistical models that are commonly used to gain insight into the genetic architecture of agronomically important traits., (© 2022 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from March 2020 to April 2021 using genomic surveillance. During this period, there were 23 distinct variants, including Beta and Gamma, among which the Gamma and related lineages were predominant in the second pandemic wave within SC. A regionalization of P.1-like-II in the Western SC region was observed, concomitant to the increase in cases, mortality, and the case fatality rate (CFR) index. This is the first evidence of the regionalization of the SARS-CoV-2 transmission in SC and it highlights the importance of tracking the variants, dispersion, and impact of SARS-CoV-2 on the public health systems.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages may impact COVID-19 disease progression and provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well phylogenetically defined, but two main factors have precluded major coinfection/codetection and recombination analysis thus far: (i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic, which limited the identification of lineage defining mutations necessary to distinguish coinfecting/recombining viral lineages; and the (ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we assembled a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. This approach enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations, representing 0.61 % of all samples investigated. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming its plausibility with the cocirculating lineages at the timeframe investigated. Our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, although it is certainly a lower bound estimate considering the difficulty to detect coinfections with very similar SARS-CoV-2 lineages and the low number of samples sequenced from the total number of infections.

One of the most remarkable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) features is the significant number of mutations they acquired. However, the specific factors that drove the emergence of such variants since the second half of 2020 are not fully resolved. In this study, we describe a new SARS-CoV-2 P.1 sub-lineage circulating in Brazil, denoted here as Gamma-like-II, that as well as the previously described lineage Gamma-like-I shares several lineage-defining mutations with the VOC Gamma. Reconstructions of ancestor sequences support that most lineage-defining mutations of the Spike (S) protein, including those at the receptor-binding domain (RBD), accumulated at the first P.1 ancestor. In contrast, mutations outside the S protein were mostly fixed at subsequent steps. Our evolutionary analyses estimate that P.1-ancestral strains carrying RBD mutations of concern probably circulated cryptically in the Amazonas for several months before the emergence of the VOC Gamma. Unlike the VOC Gamma, the other P.1 sub-lineages displayed a much more restricted dissemination and accounted for a low fraction (<2 per cent) of SARS-CoV-2 infections in Brazil in 2021. The stepwise diversification of lineage P.1 through multiple inter-host transmissions is consistent with the hypothesis that partial immunity acquired from natural SARS-CoV-2 infections in heavily affected regions might have been a major driving force behind the natural selection of some VOCs. The lag time between the emergence of the P.1 ancestor and the expansion of the VOC Gamma and the divergent epidemic trajectories of P.1 sub-lineages support a complex interplay between the emergence of mutations of concern and viral spread in Brazil., (© The Author(s) 2021. Published by Oxford University Press.)

Stomata allow CO2 uptake by leaves for photosynthetic assimilation at the cost of water vapor loss to the atmosphere. The opening and closing of stomata in response to fluctuations in light intensity regulate CO2 and water fluxes and are essential for maintaining water-use efficiency (WUE). However, a little is known about the genetic basis for natural variation in stomatal movement, especially in C4 crops. This is partly because the stomatal response to a change in light intensity is difficult to measure at the scale required for association studies. Here, we used high-throughput thermal imaging to bypass the phenotyping bottleneck and assess 10 traits describing stomatal conductance (gs) before, during and after a stepwise decrease in light intensity for a diversity panel of 659 sorghum (Sorghum bicolor) accessions. Results from thermal imaging significantly correlated with photosynthetic gas exchange measurements. gs traits varied substantially across the population and were moderately heritable (h2 up to 0.72). An integrated genome-wide and transcriptome-wide association study identified candidate genes putatively driving variation in stomatal conductance traits. Of the 239 unique candidate genes identified with the greatest confidence, 77 were putative orthologs of Arabidopsis (Arabidopsis thaliana) genes related to functions implicated in WUE, including stomatal opening/closing (24 genes), stomatal/epidermal cell development (35 genes), leaf/vasculature development (12 genes), or chlorophyll metabolism/photosynthesis (8 genes). These findings demonstrate an approach to finding genotype-to-phenotype relationships for a challenging trait as well as candidate genes for further investigation of the genetic basis of WUE in a model C4 grass for bioenergy, food, and forage production., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Sorghum (Sorghum bicolor) is a model C4 crop made experimentally tractable by extensive genomic and genetic resources. Biomass sorghum is studied as a feedstock for biofuel and forage. Mechanistic modeling suggests that reducing stomatal conductance (gs) could improve sorghum intrinsic water use efficiency (iWUE) and biomass production. Phenotyping to discover genotype-to-phenotype associations remains a bottleneck in understanding the mechanistic basis for natural variation in gs and iWUE. This study addressed multiple methodological limitations. Optical tomography and a machine learning tool were combined to measure stomatal density (SD). This was combined with rapid measurements of leaf photosynthetic gas exchange and specific leaf area (SLA). These traits were the subject of genome-wide association study and transcriptome-wide association study across 869 field-grown biomass sorghum accessions. The ratio of intracellular to ambient CO2 was genetically correlated with SD, SLA, gs, and biomass production. Plasticity in SD and SLA was interrelated with each other and with productivity across wet and dry growing seasons. Moderate-to-high heritability of traits studied across the large mapping population validated associations between DNA sequence variation or RNA transcript abundance and trait variation. A total of 394 unique genes underpinning variation in WUE-related traits are described with higher confidence because they were identified in multiple independent tests. This list was enriched in genes whose Arabidopsis (Arabidopsis thaliana) putative orthologs have functions related to stomatal or leaf development and leaf gas exchange, as well as genes with nonsynonymous/missense variants. These advances in methodology and knowledge will facilitate improving C4 crop WUE., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Stomata are adjustable pores on leaf surfaces that regulate the tradeoff of CO2 uptake with water vapor loss, thus having critical roles in controlling photosynthetic carbon gain and plant water use. The lack of easy, rapid methods for phenotyping epidermal cell traits have limited discoveries about the genetic basis of stomatal patterning. A high-throughput epidermal cell phenotyping pipeline is presented here and used for quantitative trait loci (QTL) mapping in field-grown maize (Zea mays). The locations and sizes of stomatal complexes and pavement cells on images acquired by an optical topometer from mature leaves were automatically determined. Computer estimated stomatal complex density (SCD; R2 = 0.97) and stomatal complex area (SCA; R2 = 0.71) were strongly correlated with human measurements. Leaf gas exchange traits were genetically correlated with the dimensions and proportions of stomatal complexes (rg = 0.39-0.71) but did not correlate with SCD. Heritability of epidermal traits was moderate to high (h2 = 0.42-0.82) across two field seasons. Thirty-six QTL were consistently identified for a given trait in both years. Twenty-four clusters of overlapping QTL for multiple traits were identified, with univariate versus multivariate single marker analysis providing evidence consistent with pleiotropy in multiple cases. Putative orthologs of genes known to regulate stomatal patterning in Arabidopsis (Arabidopsis thaliana) were located within some, but not all, of these regions. This study demonstrates how discovery of the genetic basis for stomatal patterning can be accelerated in maize, a C4 model species where these processes are poorly understood., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141-144, ∆211, and ∆256-258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern., (© The Author(s) 2021. Published by Oxford University Press.)

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD) is the closest animal model available to the human situation. This paradigm induces long lasting behavioral effects, causes changes in the HPA axis and affects the immune system. However, the mechanisms underlying changes in the immune response after ELA are still not fully understood. In this study we investigated how ELA changes the immune system, through an unbiased analysis, viSNE, and addressed specially the NK immune cell population and its functionality. We have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells' profile and response to target cell lines are significantly changed after ELA. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. These results suggest that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fernandes, Patil, Meriaux, Theresine, Muller, Leenen, Elwenspoek, Zimmer and Turner.)

Purpose: To explore the barriers to family resilience in caregivers of people who have schizophrenia., Design: A qualitative descriptive approach was used., Methods: Semistructured interviews were conducted with family caregivers of patients with schizophrenia registered at the psychiatry outpatient unit of a hospital center. Content analysis was performed on audio-recorded and verbatim-transcribed interviews. The consolidated criteria for reporting qualitative research (COREQ) checklist was applied to this study., Results: A total of 31 family caregivers participated, the majority of whom were female (71%) with an average age of 57.5 years. Most participants lived with and cared for their relative (90.3%). The caregiver role was assumed mostly by mothers (54.8%) and fathers (22.6%). Barriers to family resilience in caregivers of people experiencing schizophrenia broadly fall under five categories: lack of knowledge about the disease, social stigma, expressed emotion, involvement in the relationship, and blame., Conclusions: In view of the paucity of studies exploring and understanding the barriers to family resilience, this study presents itself as one of the first in this area. There are different barriers to family resilience. This research provides an overview and an understanding of key barriers to family resilience in caregivers of people experiencing schizophrenia., Clinical Relevance: There is a need for nurses to help families to be resilient. By understanding the barriers to resilience, nurses are able to focus on these factors and help families to remove or reduce their influence., (© 2021 The Authors. Journal of Nursing Scholarship published by Wiley Periodicals LLC on behalf of Sigma Theta Tau International.)

Previous studies have found that maximum quantum yield of CO2 assimilation (Φ CO2,max,app) declines in lower canopies of maize and miscanthus, a maladaptive response to self-shading. These observations were limited to single genotypes, leaving it unclear whether the maladaptive shade response is a general property of this C4 grass tribe, the Andropogoneae. We explored the generality of this maladaptation by testing the hypothesis that erect leaf forms (erectophiles), which allow more light into the lower canopy, suffer less of a decline in photosynthetic efficiency than drooping leaf (planophile) forms. On average, Φ CO2,max,app declined 27% in lower canopy leaves across 35 accessions, but the decline was over twice as great in planophiles than in erectophiles. The loss of photosynthetic efficiency involved a decoupling between electron transport and assimilation. This was not associated with increased bundle sheath leakage, based on 13C measurements. In both planophiles and erectophiles, shaded leaves had greater leaf absorptivity and lower activities of key C4 enzymes than sun leaves. The erectophile form is considered more productive because it allows a more effective distribution of light through the canopy to support photosynthesis. We show that in sorghum, it provides a second benefit, maintenance of higher Φ CO2,max,app to support efficient use of that light resource., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

DNA methylation is one of the most important epigenetic modifications and is closely related with several biological processes such as regulation of gene transcription and the development of non-malignant diseases. The prevailing dogma states that DNA methylation in eukaryotes occurs essentially through 5-methylcytosine (5mC) but recently adenine methylation was also found to be present in eukaryotes. In mouse embryonic stem cells, 6-methyladenine (6mA) was associated with the repression and silencing of genes, particularly in the X-chromosome, known to play an important role in cell fate determination. Here, we have demonstrated that 6mA is a ubiquitous eukaryotic epigenetic modification that is put in place during epigenetically sensitive periods such as embryogenesis and fetal development. In somatic cells there are clear tissue specificity in 6mA levels, with the highest 6mA levels being observed in the brain. In zebrafish, during the first 120 h of embryo development, from a single pluripotent cell to an almost fully formed individual, 6mA levels steadily increase. An identical pattern was observed over embryonic days 7-21 in the mouse. Furthermore, exposure to a neurotoxic environmental pollutant during the same early life period may led to a decrease in the levels of this modification in female rats. The identification of the periods during which 6mA epigenetic marks are put in place increases our understanding of this mammalian epigenetic modification, and raises the possibility that it may be associated with developmental processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fernandes, Grova, Roth, Duca, Godderis, Guebels, Mériaux, Lumley, Bouillaud-Kremarik, Ernens, Devaux, Schroeder and Turner.)

There is a need to increase older adults' access and adherence to falls prevention strategies. This study aims to explore older adults' perceived barriers to participation in a fall prevention strategy. A qualitative descriptive approach was used. Semi-structured interviews were conducted with 18 older adult users of a Day Care Unit from a Private Institution of Social Solidarity in the region of Lisbon and Tagus Valley in Portugal. The recruitment was made in September 2019. The interviews were recorded transcribed verbatim and analysed thematically using the method of constant comparisons. The barriers to participation in a fall prevention strategy are healthcare system gaps, social context, economic context, health status, psychological capability, and lack of knowledge to demystify myths and misconceptions about falls. There are different barriers to participate in a fall prevention strategy. It is urgent to eliminate or reduce the effect of these barriers to increase older adults' participation in fall prevention strategies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic in Brazil was dominated by two lineages designated as B.1.1.28 and B.1.1.33. The two SARS-CoV-2 variants harboring mutations at the receptor-binding domain of the Spike (S) protein, designated as lineages P.1 and P.2, evolved from lineage B.1.1.28 and are rapidly spreading in Brazil. Lineage P.1 is considered a Variant of Concern (VOC) because of the presence of multiple mutations in the S protein (including K417T, E484K, N501Y), while lineage P.2 only harbors mutation S:E484K and is considered a Variant of Interest (VOI). On the other hand, epidemiologically relevant B.1.1.33 deriving lineages have not been described so far. Here we report the identification of a new SARS-CoV-2 VOI within lineage B.1.1.33 that also harbors mutation S:E484K and was detected in Brazil between November 2020 and February 2021. This VOI displayed four non-synonymous lineage-defining mutations (NSP3:A1711V, NSP6:F36L, S:E484K, and NS7b:E33A) and was designated as lineage N.9. The VOI N.9 probably emerged in August 2020 and has spread across different Brazilian states from the Southeast, South, North, and Northeast regions.

A previous study demonstrates that most of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Brazilian strains fell in three local clades that were introduced from Europe around late February 2020. Here we investigated in more detail the origin of the major and most widely disseminated SARS-CoV-2 Brazilian lineage B.1.1.33. We recovered 190 whole viral genomes collected from 13 Brazilian states from February 29 to April 31, 2020 and combined them with other B.1.1 genomes collected globally. Our genomic survey confirms that lineage B.1.1.33 is responsible for a variable fraction of the community viral transmissions in Brazilian states, ranging from 2% of all SARS-CoV-2 genomes from Pernambuco to 80% of those from Rio de Janeiro. We detected a moderate prevalence (5-18%) of lineage B.1.1.33 in some South American countries and a very low prevalence (<1%) in North America, Europe, and Oceania. Our study reveals that lineage B.1.1.33 evolved from an ancestral clade, here designated B.1.1.33-like, that carries one of the two B.1.1.33 synapomorphic mutations. The B.1.1.33-like lineage may have been introduced from Europe or arose in Brazil in early February 2020 and a few weeks later gave origin to the lineage B.1.1.33. These SARS-CoV-2 lineages probably circulated during February 2020 and reached all Brazilian regions and multiple countries around the world by mid-March, before the implementation of air travel restrictions in Brazil. Our phylodynamic analysis also indicates that public health interventions were partially effective to control the expansion of lineage B.1.1.33 in Rio de Janeiro because its median effective reproductive number ( R e ) was drastically reduced by about 66% during March 2020, but failed to bring it to below one. Continuous genomic surveillance of lineage B.1.1.33 might provide valuable information about epidemic dynamics and the effectiveness of public health interventions in some Brazilian states., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Resende, Delatorre, Gräf, Mir, Motta, Appolinario, Paixão, Mendonça, Ogrzewalska, Caetano, Wallau, Docena, Santos, de Almeida Ferreira, Sousa Junior, Silva, Fernandes, Vianna, Souza, Ferro, Nardy, Santos, Riediger, do Carmo Debur, Croda, Oliveira, Abreu, Bello and Siqueira.)

Quantification of the simultaneous contributions of loci to multiple traits, a phenomenon called pleiotropy, is facilitated by the increased availability of high-throughput genotypic and phenotypic data. To understand the prevalence and nature of pleiotropy, the ability of multivariate and univariate genome-wide association study (GWAS) models to distinguish between pleiotropic and non-pleiotropic loci in linkage disequilibrium (LD) first needs to be evaluated. Therefore, we used publicly available maize and soybean genotypic data to simulate multiple pairs of traits that were either (i) controlled by quantitative trait nucleotides (QTNs) on separate chromosomes, (ii) controlled by QTNs in various degrees of LD with each other, or (iii) controlled by a single pleiotropic QTN. We showed that multivariate GWAS could not distinguish between QTNs in LD and a single pleiotropic QTN. In contrast, a unique QTN detection rate pattern was observed for univariate GWAS whenever the simulated QTNs were in high LD or pleiotropic. Collectively, these results suggest that multivariate and univariate GWAS should both be used to infer whether or not causal mutations underlying peak GWAS associations are pleiotropic. Therefore, we recommend that future studies use a combination of multivariate and univariate GWAS models, as both models could be useful for identifying and narrowing down candidate loci with potential pleiotropic effects for downstream biological experiments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fernandes, Zhang, Jamann and Lipka.)

Sorghum and maize share a close evolutionary history that can be explored through comparative genomics 1,2 . To perform a large-scale comparison of the genomic variation between these two species, we analysed ~13 million variants identified from whole-genome resequencing of 499 sorghum lines together with 25 million variants previously identified in 1,218 maize lines. Deleterious mutations in both species were prevalent in pericentromeric regions, enriched in non-syntenic genes and present at low allele frequencies. A comparison of deleterious burden between sorghum and maize revealed that sorghum, in contrast to maize, departed from the domestication-cost hypothesis that predicts a higher deleterious burden among domesticates compared with wild lines. Additionally, sorghum and maize population genetic summary statistics were used to predict a gene deleterious index with an accuracy greater than 0.5. This research represents a key step towards understanding the evolutionary dynamics of deleterious variants in sorghum and provides a comparative genomics framework to start prioritizing these variants for removal through genome editing and breeding.

Background: Advances in genotyping and phenotyping techniques have enabled the acquisition of a great amount of data. Consequently, there is an interest in multivariate statistical analyses that identify genomic regions likely to contain causal mutations affecting multiple traits (i.e., pleiotropy). As the demand for multivariate analyses increases, it is imperative that optimal tools are available to assess their performance. To facilitate the testing and validation of these multivariate approaches, we developed simplePHENOTYPES, an R/CRAN package that simulates pleiotropy, partial pleiotropy, and spurious pleiotropy in a wide range of genetic architectures, including additive, dominance and epistatic models., Results: We illustrate simplePHENOTYPES' ability to simulate thousands of phenotypes in less than one minute. We then provide two vignettes illustrating how to simulate sets of correlated traits in simplePHENOTYPES. Finally, we demonstrate the use of results from simplePHENOTYPES in a standard GWAS software, as well as the equivalence of simulated phenotypes from simplePHENOTYPES and other packages with similar capabilities., Conclusions: simplePHENOTYPES is a R/CRAN package that makes it possible to simulate multiple traits controlled by loci with varying degrees of pleiotropy. Its ability to interface with both commonly-used marker data formats and downstream quantitative genetics software and packages should facilitate a rigorous assessment of both existing and emerging statistical GWAS and GS approaches. simplePHENOTYPES is also available at https://github.com/samuelbfernandes/simplePHENOTYPES .

Herbicide application is crucial for weed management in most crop production systems, but for sorghum herbicide options are limited. Sorghum is sensitive to residual protoporphyrinogen oxidase (PPO)-inhibiting herbicides, such as fomesafen, and a long re-entry period is required before sorghum can be planted after its application. Improving sorghum for tolerance to such residual herbicides would allow for increased sorghum production and the expansion of herbicide options for growers. In this study, we observed sorghum tolerance to residual fomesafen. To investigate the underlying tolerance mechanism a genome-wide association mapping study was conducted using field-collected sorghum biomass panel (SBP) data, and a greenhouse assay was developed to confirm the field phenotypes. A total of 26 significant SNPs (FDR<0.05), spanning a 215.3 kb region on chromosome 3, were detected. The ten most significant SNPs included two in genic regions (Sobic.003G136800, and Sobic.003G136900) and eight SNPs in the intergenic region encompassing the genes Sobic.003G136700, Sobic.003G136800, Sobic.003G137000, Sobic.003G136900, and Sobic.003G137100. The gene Sobic.003G137100 (PPXI), which encodes the PPO1 enzyme, one of the targets of PPO-inhibiting herbicides, was located 12kb downstream of the significant SNP S03&#95;13152838. We found that PPXI is highly conserved in sorghum and expression does not significantly differ between tolerant and sensitive sorghum lines. Our results suggest that PPXI most likely does not underlie the observed herbicide tolerance. Instead, the mechanism underlying herbicide tolerance in the SBP is likely metabolism-based resistance, possibly regulated by the action of multiple genes. Further research is necessary to confirm candidate genes and their functions., Competing Interests: The authors have declared that no competing interests exist.

Spectral quality is an important factor for in vitro development of explants in a bioreactor system. Based on the need to optimize micropropagation for E. grandis  ×  E. urophylla clones, the aim of the study was to assess the spectral quality of in vitro multiplication in temporary immersion bioreactor (TIB). The tissue used to generate the explants (i.e., the nodal segment with 1 cm of length and two axillary bud without leaves) was previously in vitro established and multiplied , it derived from ministumps of E. grandis  ×  E. urophylla clone grown in a semi-hydroponic system. The spectral quality of in vitro multiplication was assessed through five light sources (i.e., fluorescent lamp, red, green, blue, and yellow cellophane). Morphological and anatomical features of tissues grown in TIB were evaluated at 90 days. Based on the results, yellow and blue spectral qualities were the most suitable to be adopted for in vitro multiplication of E. grandis  ×  E. urophylla , since they enabled lesser hyperhydricity, favors high number of shoots per explant and shoot length, as well as thicker mesophyll and spongy parenchyma; arise as an alternative for large-scale production of eucalypts clonal plants., Competing Interests: Conflicts of interest/Competing interestsNot applicable' for that section., (© King Abdulaziz City for Science and Technology 2020.)

Early life adversity (ELA) has been associated with inflammation and immunosenescence, as well as hyporeactivity of the HPA axis. Because the immune system and the HPA axis are tightly intertwined around the glucocorticoid receptor (GR), we examined peripheral GR functionality in the EpiPath cohort among participants who either had been exposed to ELA (separation from parents and/or institutionalization followed by adoption; n = 40) or had been reared by their biological parents (n = 72).Expression of the strict GR target genes FKBP5 and GILZ as well as total and 1F and 1H GR transcripts were similar between groups. Furthermore, there were no differences in GR sensitivity, examined by the effects of dexamethasone on IL6 production in LPS-stimulated whole blood. Although we did not find differences in methylation at the GR 1F exon or promoter region, we identified a region of the GR 1H promoter (CpG 1-9) that showed lower methylation levels in ELA.Our results suggest that peripheral GR signaling was unperturbed in our cohort and the observed immune phenotype does not appear to be secondary to an altered GR response to the perturbed HPA axis and glucocorticoid (GC) profile, although we are limited in our measures of GR activity and time points.

Maize inflorescence is a complex phenotype that involves the physical and developmental interplay of multiple traits. Given the evidence that genes could pleiotropically contribute to several of these traits, we used publicly available maize data to assess the ability of multivariate genome-wide association study (GWAS) approaches to identify pleiotropic quantitative trait loci (pQTL). Our analysis of 23 publicly available inflorescence and leaf-related traits in a diversity panel of n = 281 maize lines genotyped with 376,336 markers revealed that the two multivariate GWAS approaches we tested were capable of identifying pQTL in genomic regions coinciding with similar associations found in previous studies. We then conducted a parallel simulation study on the same individuals, where it was shown that multivariate GWAS approaches yielded a higher true-positive quantitative trait nucleotide (QTN) detection rate than comparable univariate approaches for all evaluated simulation settings except for when the correlated simulated traits had a heritability of 0.9. We therefore conclude that the implementation of state-of-the-art multivariate GWAS approaches is a useful tool for dissecting pleiotropy and their more widespread implementation could facilitate the discovery of genes and other biological mechanisms underlying maize inflorescence., (© The Author(s) 2020. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.

Background: Exserohilum turcicum is an important pathogen of both sorghum and maize, causing sorghum leaf blight and northern corn leaf blight. Because the same pathogen can infect and cause major losses for two of the most important grain crops, it is an ideal pathosystem to study plant-pathogen evolution and investigate shared resistance mechanisms between the two plant species. To identify sorghum genes involved in the E. turcicum response, we conducted a genome-wide association study (GWAS)., Results: Using the sorghum conversion panel evaluated across three environments, we identified a total of 216 significant markers. Based on physical linkage with the significant markers, we detected a total of 113 unique candidate genes, some with known roles in plant defense. Also, we compared maize genes known to play a role in resistance to E. turcicum with the association mapping results and found evidence of genes conferring resistance in both crops, providing evidence of shared resistance between maize and sorghum., Conclusions: Using a genetics approach, we identified shared genetic regions conferring resistance to E. turcicum in both maize and sorghum. We identified several promising candidate genes for resistance to leaf blight in sorghum, including genes related to R-gene mediated resistance. We present significant advancements in the understanding of host resistance to E. turcicum, which is crucial to reduce losses due to this important pathogen.

The ability to connect genetic information between traits over time allow Bayesian networks to offer a powerful probabilistic framework to construct genomic prediction models. In this study, we phenotyped a diversity panel of 869 biomass sorghum ( Sorghum bicolor (L.) Moench) lines, which had been genotyped with 100,435 SNP markers, for plant height (PH) with biweekly measurements from 30 to 120 days after planting (DAP) and for end-of-season dry biomass yield (DBY) in four environments. We evaluated five genomic prediction models: Bayesian network (BN), Pleiotropic Bayesian network (PBN), Dynamic Bayesian network (DBN), multi-trait GBLUP (MTr-GBLUP), and multi-time GBLUP (MTi-GBLUP) models. In fivefold cross-validation, prediction accuracies ranged from 0.46 (PBN) to 0.49 (MTr-GBLUP) for DBY and from 0.47 (DBN, DAP120) to 0.75 (MTi-GBLUP, DAP60) for PH. Forward-chaining cross-validation further improved prediction accuracies of the DBN, MTi-GBLUP and MTr-GBLUP models for PH (training slice: 30-45 DAP) by 36.4-52.4% relative to the BN and PBN models. Coincidence indices (target: biomass, secondary: PH) and a coincidence index based on lines (PH time series) showed that the ranking of lines by PH changed minimally after 45 DAP. These results suggest a two-level indirect selection method for PH at harvest (first-level target trait) and DBY (second-level target trait) could be conducted earlier in the season based on ranking of lines by PH at 45 DAP (secondary trait). With the advance of high-throughput phenotyping technologies, our proposed two-level indirect selection framework could be valuable for enhancing genetic gain per unit of time when selecting on developmental traits., (Copyright © 2020 dos Santos et al.)

Sorghum ( Sorghum bicolor L.) is a major food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. The lack of recombination, drift, and the coupling with favorable loci impede the removal of deleterious mutations from the genome by selection. To study how deleterious variants impact phenotypes, we identified putative deleterious mutations among ∼5.5 M segregating variants of 229 diverse biomass sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that ∼33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups. Across racial groups, the mutation burden correlated negatively with biomass, plant height, specific leaf area (SLA), and tissue starch content (TSC), suggesting that deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly one-half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (average of 3.1% across all stages). There is no advantage in total heritable variance for SLA and TSC. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, these results suggest that incorporating putatively deleterious variants into genomic models slightly improves prediction accuracy because of extensive linkage. Knowledge of deleterious variants could be leveraged for sorghum breeding through either genome editing and/or conventional breeding that focuses on the selection of progeny with fewer deleterious alleles., (Copyright © 2019 by the Genetics Society of America.)

We have previously hypothesized that relatively small and isolated rural communities may experience founder effects, defined as the genetic ramifications of small population sizes at the time of a community's establishment. To explore this, we used an Illumina Infinium Omni2.5Exome-8 chip to collect data from 157 individuals from four Illinois communities, three rural and one urban. Genetic diversity estimates of 999,259 autosomal markers suggested that the reduction in heterozygosity due to shared ancestry was approximately 0, indicating a randomly mating population. An eigenanalysis, which is similar to a principal component analysis but run on a genetic coancestry matrix, conducted in the SNPRelate R package revealed that most of these individuals formed one cluster, with a few putative outliers obscuring population variation. An additional eigenanalysis on the same markers in a combined data set including the 2,504 individuals in the 1000 Genomes database found that most of the 157 Illinois individuals clustered into one group in close proximity to individuals of European descent. A final eigenanalysis of the Illinois individuals with the 503 individuals of European descent (within the 1000 Genomes Project) revealed two clusters of individuals and likely two source populations; one British and one consisting of multiple European subpopulations. We therefore demonstrate the feasibility of examining genetic relatedness across Illinois populations and assessing the number of source populations using publicly available databases. When assessed, population structure information can contribute to the understanding of genetic history in rural populations.

Key Message: We compare genomic selection methods that use correlated traits to help predict biomass yield in sorghum, and find that trait-assisted genomic selection performs best. Genomic selection (GS) is usually performed on a single trait, but correlated traits can also help predict a focal trait through indirect or multi-trait GS. In this study, we use a pre-breeding population of biomass sorghum to compare strategies that use correlated traits to improve prediction of biomass yield, the focal trait. Correlated traits include moisture, plant height measured at monthly intervals between planting and harvest, and the area under the growth progress curve. In addition to single- and multi-trait direct and indirect GS, we test a new strategy called trait-assisted GS, in which correlated traits are used along with marker data in the validation population to predict a focal trait. Single-trait GS for biomass yield had a prediction accuracy of 0.40. Indirect GS performed best using area under the growth progress curve to predict biomass yield, with a prediction accuracy of 0.37, and did not differ from indirect multi-trait GS that also used moisture information. Multi-trait GS and single-trait GS yielded similar results, indicating that correlated traits did not improve prediction of biomass yield in a standard GS scenario. However, trait-assisted GS increased prediction accuracy by up to [Formula: see text] when using plant height in both the training and validation populations to help predict yield in the validation population. Coincidence between selected genotypes in phenotypic and genomic selection was also highest in trait-assisted GS. Overall, these results suggest that trait-assisted GS can be an efficient strategy when correlated traits are obtained earlier or more inexpensively than a focal trait.

Introduction: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015., Methods: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions. The HIV pol genotypic test was performed by genomic sequencing., Results: We analysed samples from 1568 antiretroviral-naive individuals recently diagnosed with HIV, and the overall transmitted drug resistance (TDR) prevalence was 9.5% (150 sequences). The regional prevalence of resistance according to Brazilian geographical regions was 9.4% in the northeast, 11.2% in the southeast, 6.8% in the central region, 10.2% in the north and 8.8% in the south. The inhibitor-specific TDR prevalence was 3.6% for nucleoside reverse transcriptase inhibitors (NRTIs), 5.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 1.6% for protease inhibitors (PIs); 1.0% of individuals presented resistance to more than one class of inhibitors. Overall, subtype B was more prevalent in every region except for the southern, where subtype C prevails., Conclusions: To the best of our knowledge, this is the first TDR study conducted in Brazil with nationwide representative sampling. The TDR prevalence revealed a moderate rate in the five Brazilian geographical regions, although some cities presented higher TDR prevalence rates, reaching 14% in São Paulo, for example. These results further illustrate the importance of surveillance studies for designing future strategies in primary antiretroviral therapy, aiming to mitigate TDR, as well as for predicting future trends in other regions of the globe where mass antiretroviral (ARV) treatment was implemented., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Unlabelled: Connective tissue graft (CTG), which is considered to be among the best techniques for treating gingival recession, has presented stable long-term results. However, this technique causes morbidity and discomfort in the palatine region due to graft removal at that site. A previous study reports that photobiomodulation (PBM) using a dosage of 15 J/cm(2) may improve wound healing and the patient's postoperative comfort. However, no other studies in the literature provide the best application dosage or comparisons between protocols for this purpose. The aim of this study is to compare two power densities of PBM on the wound-healing process of the donor palatine area after CTG removal. In this study, 51 patients presenting buccal gingival recession were randomized into one of the following groups: group 1: CTG procedure for root coverage and PBM application at the donor site using a 60 J/cm(2) dose; group 2: CTG and PBM application using a 30 J/cm(2) dose; or group 3: CTG and sham application. The evaluated parameters were the wound remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT), and postoperative discomfort (D), evaluated at baseline and 7, 14, 45, 60, and 90 days after surgery. Group 1 presented statistically significant smaller wounds at day 7 (p > 0.05). None of the patients presented scars at the operated area, and all of the patients reported mild discomfort, with low consumption of analgesic pills. We concluded that the protocol of 60 J/cm(2) provided faster wound healing 7 days after removing the connective tissue graft for root coverage., Trial Registration: ClinicalTrial.org (NCT02580357) https://clinicaltrials.gov/ct2/show/NCT02580357 .

Adverse reactions related to ethanolamine oleate (EO) include pain during injection, redness, inflammation, tissue necrosis, and allergic reaction. The authors report a patient of exuberant facial edema after the injection of EO used in sclerotherapy of lip hemangioma in a child. A 9-year-old boy was referred to authors' oral and maxillofacial surgery unit to treat a vascular lesion of the upper lip. The lesion has causing enlargement of the middle area of the upper lip, being sessile and resilient by palpation. It was decided to employ sclerotherapy aiming to reduce the size for posterior surgical excision of the residual lesion. The day after the injection, the patient presented intense edema limited to the upper lip, complaining of mild pain. Although side effects reported of EO injection are mild and with almost no clinical significance, major complications like anaphylaxis and severe edema can occur, such in the patient here presented.

The common bean is a food with high mineral content. Of the various types of beans cultivated in Brazil, carioca type beans are the most consumed. The aim of this study was to identify promising common bean populations with an emphasis toward the selection of carioca type bean lines with high calcium content. We also aimed to verify whether and how the crop season and the genotype (parental line and hybrid populations) x crop season interaction affect calcium content. A group of 3 lines of good agronomic characteristics were crossed with a group of 4 lines with high calcium content in a 3 x 4 partial diallel design. Great variability was identified among both the parental lines and the hybrid populations derived from the diallel crosses among the parental lines. We found significant interactions between crop season and both parental line and hybrid population. In the diallel analysis, only the general combining ability was significant, explaining 89.4% of the sum of squares. The RP-1, CNF05, and Safira lines exhibited the greatest calcium contents and a positive GCA. RP-1 is a line that presents high calcium content, in addition to having carioca type beans and an upright plant with high yield. To further increase the calcium content of the RP-1 line, we suggest crossing it with the CNF05 and Safira lines. Although there was a hybrid population x crop season interaction, it was possible to identify populations that performed best in terms of calcium content in both crop seasons.

The isolated zygomatic arch fractures represent 21% of zygomatic-maxillary fractures and the falls is the main etiology. This type of fracture is easily reduced through several methods and the most used is the reduction through the surgical temporal approach of Gillies. The present patient illustrates the success treatment of a patient with isolated zygomatic arch fracture which a Foley catheter was used to stabilize the fracture reduction.

Patients with cleft palate and cleft lip have severe functional and aesthetic problems, if this deformity is not treated properly and in time, can also cause psychological and aesthetic problems to the patients. This study reports a case of a 22-year-old patient with incomplete bilateral cleft lip, addressing aspects related to the diagnosis, treatment planning, surgical technique, and postoperative follow-up of the patient. Surgical treatment of cleft lip and cleft palate consists of suturing the lip and the palate, and aims not only the aesthetic restoration, but also the recovery of the phonation, mastication and respiration, as well as a normal psychosocial development.

The aim of this study was to undertake the theoretical derivations of non-parametric methods, which use linear regressions based on rank order, for stability analyses. These methods were extension different parametric methods used for stability analyses and the result was compared with a standard non-parametric method. Intensive computational methods (e.g., bootstrap and permutation) were applied, and data from the plant-breeding program of the Biology Department of UFLA (Minas Gerais, Brazil) were used to illustrate and compare the tests. The non-parametric stability methods were effective for the evaluation of phenotypic stability. In the presence of variance heterogeneity, the non-parametric methods exhibited greater power of discrimination when determining the phenotypic stability of genotypes.

The 2009 pandemic influenza A virus outbreak led to the systematic use of the neuraminidase (NA) inhibitor oseltamivir (OST). Consequently, OST-resistant strains, carrying the mutation H275Y, emerged in the years after the pandemics, with a prevalence of 1-2%. Currently, OST-resistant strains have been found in community settings, in untreated individuals. To spread in community settings, H275Y mutants must contain additional mutations, collectively called permissive mutations. We display the permissive mutations in NA of OST-resistant A(H1N1)pdm09 virus found in Brazilian community settings. The NAs from 2013 are phylogenetically distinct from those of 2012, indicating a tendency of positive selection of NAs with better fitness. Some previously predicted permissive mutations, such as V241I and N369K, found in different countries, were also detected in Brazil. Importantly, the change D344N, also predicted to compensate loss of fitness imposed by H275Y mutation, was found in Brazil, but not in other countries in 2013. Our results reinforce the notion that OST-resistant A(H1N1)pdm09 strains with compensatory mutations may arise in an independent fashion, with samples being identified in different states of Brazil and in different countries. Systematic circulation of these viral strains may jeopardise the use of the first line of anti-influenza drugs in the future.

Purpose: To evaluate the esthetic outcome of four different approaches to treat gingival recession, associated with non-carious cervical lesion (combined defects) and the possible roles of patient-related factors in this esthetic outcome., Methods: 78 combined defects were previously treated by: coronally advanced flap (CAF), CAF plus cervical restoration using resin-modified glass-ionomer material (CAF+R), connective tissue graft (CTG) and CTG+R. After a follow-up of 2 years, esthetic evaluations were performed using a modification of the Root Coverage Esthetic Score (MRES) and Qualitative Cosmetic Evaluation (QCE). Additionally, regression analyses were performed to evaluate the influence of patient-related factors in the final esthetic outcome., Results: The MRES showed that CAF and CTG had statistically significantly better results, when compared to the other groups (P < 0.05). Similarly, the QCE showed that CAF and CTG, along with CAF+R presented better results, and CTG+R showed the poorest esthetic outcome. Regression analyses showed that the overall gingival inflammation (full mouth bleeding index--FMBI) was negatively associated with CTG MRES score (P = 0.04 and R = -0.48). This means that the greater the FMBI during the study period, the lower the final esthetic score.