ABSTRACT
Flavonoids are secondary metabolites associated with plant seed coat and flower color. These compounds provide health benefits to humans as anti-inflammatory and antioxidant compounds. The expression of the late biosynthetic genes in the flavonoid pathway is controlled by a ternary MBW protein complex consisting of interfacing MYB, beta-helix-loop-helix (bHLH), and WD40 Repeat (WDR) proteins. P, the master regulator gene of the flavonoid expression in common bean (Phaseolus vulgaris L.), was recently determined to encode a bHLH protein. The T and Z genes control the distribution of color in bean seeds and flowers and have historically been considered regulators of the flavonoid gene expression. T and Z candidates were identified using reverse genetics based on genetic mapping, phylogenetic analysis, and mutant analysis. Domain and AlphaFold2 structure analyses determined that T encodes a seven-bladed ß-propeller WDR protein, while Z encodes a R2R3 MYB protein. Deletions and SNPs in T and Z mutants, respectively, altered the 3D structure of these proteins. Modeling of the Z MYB/P bHLH/T WDR MBW complex identified interfacing sequence domains and motifs in all three genes that are conserved in dicots. One Z MYB motif is a possible beta-molecular recognition feature (ß-MoRF) that only appears in a structured state when Z MYB is modeled as a component of a MBW complex. Complexes containing mutant T and Z proteins changed the interaction of members of the complex in ways that would alter their role in regulating the expression of genes in the flavonoid pathway.
ABSTRACT
The present experiments examined the encoding and retrieval conditions in an item-method-directed forget (IMDF) study that included a novel control condition. In the IMDF condition, half of the items were followed by a remember cue whereas the other half were followed by a forget cue. In a remember-both control condition, half of the items were followed by an item identifier called Set A; whereas the other half of the items were followed by a Set B identifier. At the test, items were recalled as a function of the instruction cue or the set identifier. Across two experiments, directed-forgetting effects and associated benefits were found. Further, results from both studies revealed a new way to demonstrate the benefit of IMDF - directed-forgetting participants made more correct source attributions compared to remember-both participants. These benefits were obtained using a within-subjects IMDF paradigm (Experiment 1) as well as a between-subjects IMDF paradigm (Experiment 2). These patterns of results are consistent with several current theories of item-method-directed forgetting.
Subject(s)
Cues , Mental Recall , Humans , Male , Female , Adult , Young AdultABSTRACT
The purpose of this study was to examine adolescents' beliefs about fighting as mediators of longitudinal relations between perceptions of parental support for fighting and nonviolence and changes in adolescents' physical aggression. Participants were 2,575 middle school students (Mage = 12.20, SD = 1.02; 52% female; 83% African American) from the southeastern U.S. attending schools in communities with high rates of violence. Participants completed four waves of assessments every 3 months (i.e., fall, winter, spring, and summer). Each belief subscale mediated relations between perceptions of parental support for fighting and nonviolence and changes in aggression. Parental support for nonviolence was negatively associated with beliefs supporting reactive aggression and positively associated with beliefs against fighting. Parental support for retaliation was positively associated with beliefs supporting reactive and proactive aggression, and negatively associated with beliefs against fighting. Parental support for fighting as sometimes necessary was positively associated with beliefs supporting reactive aggression and beliefs that fighting is sometimes necessary. Beliefs supporting reactive and proactive aggression and beliefs that fighting is sometimes necessary were positively associated with aggression, whereas beliefs against fighting was negatively associated with aggression. Parents' support for fighting and for nonviolence may directly and indirectly reduce adolescents' physical aggression by influencing beliefs about the appropriateness of using aggression for self-defense and to attain a goal. This highlights the importance of jointly investigating multiple types of parental messages and types of beliefs about fighting.
Subject(s)
Adolescent Behavior , Aggression , Parent-Child Relations , Violence , Humans , Adolescent , Female , Aggression/psychology , Male , Adolescent Behavior/psychology , Child , Violence/psychology , Parenting/psychology , Parents/psychology , Longitudinal StudiesABSTRACT
Violence disproportionately impacts Black American youth, representing a major health disparity. Addressing the possible root causes of structural inequities to reduce violence may increase the impact of prevention strategies. However, efforts to evaluate the impact of such interventions pose numerous methodological challenges, particularly around selecting an effective evaluation design to detect change at the community level, with adequate power and sampling, and appropriate constructs and measurement strategies. We propose a multiple baseline experimental design to evaluate the impact of a community-level youth violence and suicidality prevention strategy. A multiple baseline experimental design with multiple community units balances the need for scientific rigor with practical and values-based considerations. It includes randomization and plausible counterfactuals without requiring large samples or placing some communities in the position of not receiving the intervention. Considerations related to the conceptualization of the logic model, mechanisms of change, and health disparity outcomes informed the development of the measurement strategy. The strengths and weaknesses of a multiple baseline experimental design are discussed in comparison to versions of randomized clinical trials. Future health disparity intervention evaluation research will benefit from (1) building a shared sense of urgent public need to promote health; (2) respecting the validity of values- and partnership-based decision-making; and (3) promoting community-based and systems-level partnerships in scientific grant funding. The described study has been registered prospectively at clinicaltrials.gov, Protocol Record 21-454.
Subject(s)
Violence , Humans , Adolescent , Violence/prevention & control , Black or African American , Program Evaluation , Research DesignABSTRACT
INTRODUCTION: This study investigates the applicability of the new metabolic dysfunction-associated steatotic liver disease (MASLD) nomenclature to the real-world TARGET-NASH US adult cohort. METHODS: The new MASLD/metabolic steatohepatitis nomenclature was applied to patients enrolled with pragmatic diagnoses of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), and NASH cirrhosis and concordance were determined between the definitions. RESULTS: Approximately 99% of TARGET-NASH participants met the new MASLD diagnostic criteria. Approximately 1,484/1,541 (96.3%, kappa 0.974) nonalcoholic fatty liver patients (metabolic dysfunction-associated steatotic liver), 2,195/2,201 (99.7%, kappa 0.998) NASH patients (metabolic steatohepatitis), and 1,999/2,003 (99.8%, kappa 0.999) NASH cirrhosis patients met the new criteria. DISCUSSION: The new MASLD nomenclature is highly concordant with the previous TARGET-NASH pragmatic definitions.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/complications , Female , Male , Middle Aged , Adult , Terminology as Topic , Liver Cirrhosis/complications , Cohort Studies , Aged , Fatty Liver/complications , United States/epidemiologyABSTRACT
OBJECTIVE: To assess the accuracy of canine intraocular pressure (IOP) estimates from the eyeTelemed IOPvet indentation tonometer. ANIMALS STUDIED: Part 1 included 54 eyes from 28 Beagle dogs-23 ADAMTS10-mutants with open-angle glaucoma and 5 normals. Part 2 involved five normal canine ex vivo globes. PROCEDURE: Part 1 (in vivo) compared IOPvet estimates in normal and glaucomatous dogs to Reichert Tono-Vera® Vet rebound tonometry. The three IOPvet estimates were green (normal; <20 mmHg, according to the manufacturer), yellow (elevated; 20-30 mmHg), and red (high; >30 mmHg). In Part 2 (ex vivo), the pressure inside freshly enucleated normal canine eyes was progressively increased from 5 to 80 mmHg and compared to IOPvet estimates. Descriptive statistics compared IOPvet estimates to rebound tonometry and direct manometry, with the threshold from normal to glaucoma set at 30 mmHg. RESULTS: In Part 1 (in vivo), normal pressures (≤30 mmHg) were mainly identified correctly as green or yellow-110 of 111 estimates, corresponding to a specificity of 99%. Only 16 of 125 affected estimates were correctly displayed in the >30-mmHg range; the remaining 109 showed ≤30 mmHg, corresponding to a sensitivity of 13%. In Part 2 (ex vivo), all normal pressures were correctly estimated with green, but 64 of 88 manometric IOPs >30 mmHg were falsely estimated as 20-30 mmHg. CONCLUSIONS: The IOPvet is inaccurate in estimating canine IOP with a low sensitivity at identifying dogs with IOP > 30 mmHg. Canine-specific instrument revision is required to correctly identify elevated (yellow = 20-30 mmHg) and high (red >30 mmHg) IOPs.
ABSTRACT
OBJECTIVE: To determine the accuracy of the Reichert® Tono-Vera® Vet rebound tonometer for canine intraocular pressure (IOP) measurement. ANIMALS STUDIED: Five normal canine ex vivo globes. PROCEDURES: The anterior chambers of five freshly enucleated normal canine eyes were cannulated and connected to a reservoir of Plasma-Lyte A and a manometer. Starting at a manometric IOP of 5 mmHg, the pressure was progressively increased to 80 mmHg by raising the reservoir. Triplicate IOP measurements were taken with the Tono-Vera® Vet from the central cornea using the dog setting and compared to the manometric pressure by linear regression analysis and Bland-Altman plots. RESULTS: There was a strong positive linear regression trend when comparing central corneal Tono-Vera® Vet IOPs to manometric pressures (r2 = .99) with solid agreement between the two methods. Compared to manometric IOPs, the Tono-Vera® Vet underestimated IOPs at higher pressures ≥70 mmHg. CONCLUSIONS: Measurement of IOPs from the central cornea with the Tono-Vera® Vet provided accurate results over a large range in normal canine globes compared to direct manometry. The mild to moderate underestimation of IOPs at high pressures was not considered clinically relevant.
Subject(s)
Intraocular Pressure , Tonometry, Ocular , Animals , Dogs/physiology , Tonometry, Ocular/veterinary , Tonometry, Ocular/instrumentation , Intraocular Pressure/physiology , Reproducibility of ResultsABSTRACT
Firearm-related injury and mortality prevention strategies are often incompatible with and potentially ineffective for the very populations at risk. Such incompatibility is reflective of a cultural disconnect between investigators and prevention specialists and those who own and use firearms. The current paper describes Project GRIP, a research study that was guided by the principles of Participatory Action Research (PAR). We present the project as a case-example and demonstration of how PAR principles can inform an approach to partner with firearm owners in injury prevention research. Though PAR is a general approach and not a set of techniques, we describe the strategies we used in the hopes that they may be useful for investigators using PAR with firearm owners. We discuss the project and our approach across different stages of the process, including entering into PAR with firearm owners, building partnerships, developing a shared vision, mutual understanding, and co-learning, building and maintaining positive relationships, and executing the project tasks. The PAR approach and the intentional emphasis on partnership is, in our opinion, vital to ensuring that the perspectives of firearm owners are incorporated into the research literature so that more ecologically valid and potentially effective injury and mortality prevention strategies can be developed and disseminated.
ABSTRACT
This mixed methods study had two aims: (1) to examine the effectiveness of a jail diversion program in reducing recidivism and promoting educational and employment outcomes; and (2) to qualitatively explore mechanisms through which the program was effective. Participants were 17 individuals arrested for drug offenses who participated in an intensive, law enforcement-based jail diversion program, and 17 individuals in a comparison group. Arrests were extracted from police records, and education and employment were extracted from program data. Four intervention participants completed qualitative interviews. Arrest rates in the intervention group decreased significantly postintervention, and arrest rates in the intervention group were numerically lower than those in the comparison group. Participants experienced significant increases in employment and driver's license status. Participants also identified mechanisms through which the program was effective. This jail diversion program shows promise in reducing recidivism and promoting adaptive functioning. Jail diversion programs that include mentorship, peer support, and removal of barriers to success may be particularly effective.
Subject(s)
Jails , Recidivism , Humans , Law Enforcement/methodsABSTRACT
Vibrio cholerae (V. cholerae), the etiological agent of cholera, uses cholera toxin (CT) to cause severe diarrheal disease. Cholera is still a significant cause of mortality worldwide with about half of all cholera cases and deaths occurring in children under five. Owing to the lack of cost-effective vaccination and poor vaccine efficacy in children, there is a need for alternative preventative and therapeutic strategies. Recent advances in our knowledge of the interplay between CT-induced disease and host-pathogen metabolism have opened the door for investigating how modulation of intestinal metabolism by V. cholerae during disease impacts host intestinal immunity, the gut microbiota, and pathogen-phage interactions. In this review article, we examine recent progress in our understanding of host-pathogen interactions during V. cholerae infection and discuss future work deciphering how modulation of gut metabolism during cholera intersects these processes to enable successful fecal-oral transmission of the pathogen.
Subject(s)
Bacteriophages , Cholera , Vibrio cholerae , Child , Humans , Vibrio cholerae/metabolism , Cholera Toxin/metabolism , Host-Pathogen Interactions , Bacteriophages/metabolismABSTRACT
Sclerotinia sclerotiorum is a necrotrophic fungal pathogen causing white mold on many important economic crops. Recently, some mycoviruses such as S. sclerotiorum hypovirulence-associated DNA virus 1 (SsHADV-1) converted S. sclerotiorum into a beneficial symbiont that helps plants manage pathogens and other stresses. To explore the potential use of SsHADV-1 as a biocontrol agent in the United States and to test the efficacy of SsHADV-1-infected United States isolates in managing white mold and other crop diseases, SsHADV-1 was transferred from the Chinese strain DT-8 to United States isolates of S. sclerotiorum. SsHADV-1 is readily transmitted horizontally among United States isolates of S. sclerotiorum and consistently conferred hypovirulence to its host strains. Biopriming of dry bean seeds with hypovirulent S. sclerotiorum strains enhanced resistance to white mold, gray mold, and Rhizoctonia root rot. To investigate the underlying mechanisms, endophytic growth of hypovirulent S. sclerotiorum in dry beans was confirmed using PCR, and the expression of 12 plant defense-related genes were monitored before and after infection. The results indicated that the endophytic growth of SsHADV-1-infected strains in plants stimulated the expression of plant immunity pathway genes that assisted a rapid response from the plant to fungal infection. Finally, application of the seed biopriming technology with SsHADV-1-infected hypervirulent strain has promise for the biological control of several diseases of wheat, pea, and sunflower.
Subject(s)
Ascomycota , Fungal Viruses , Satellite Viruses , Ascomycota/genetics , DNA Viruses/geneticsABSTRACT
Bean common mosaic virus (BCMV) and bean common mosaic necrosis virus (BCMNV) have a damaging impact on global common bean (Phaseolus vulgaris L.) cultivation, causing potential yield losses of over 80%. The primary strategy for controlling these viruses is through host plant resistance. This research aimed to identify and validate structural variations for the bc-ud gene as revealed by long-read sequencing, develop an efficient DNA marker to assist selection of bc-ud in snap and dry beans, and examine the interactions between the bc-ud allele and other BCMV resistance genes. A gene (Phvul.005G125100) model on chromosome Pv05, encoding a vacuolar protein-sorting 4 (Vps4) AAA+ ATPase endosomal sorting complexes required for transport (ESCRT) protein, was identified as the best candidate gene for bc-ud. An 84-bp repetitive insertion variant within the gene, exhibited 100% co-segregation with the bc-ud resistance allele across 264 common bean accessions. The 84-bp repetitive insertion was labeled with an indel marker IND_05_36225873 which was useful for tracking the bc-ud allele across diverse germplasm. A different single nucleotide polymorphism variant within the same candidate gene was associated with the bc-4 gene. Segregation in F2 populations confirmed bc-ud and bc-4 were alleles, so bc-4 was renamed bc-ur to fit gene nomenclature guidelines. The interactions of bc-ud and bc-ur with other resistance genes, such as bc-1 (receptor-like kinase on Pv03) and bc-2 (Vps4 AAA+ ATPase ESCRT protein on Pv11), validated gene combinations in the differential "host groups" effective against specific BCMV/BCMNV "pathogroups." These findings increase our understanding of the Bc-u locus, and enhance our ability to develop more resilient bean varieties through marker-assisted selection, reducing the impact of BCMV and BCMNV.
Subject(s)
Phaseolus , Potyvirus , Alleles , Phaseolus/genetics , Disease Resistance/genetics , Mutation , Endosomal Sorting Complexes Required for Transport/geneticsABSTRACT
KEY MESSAGE: R-BPMV is located within a recently expanded TNL cluster in the Phaseolus genus with suppressed recombination and known for resistance to multiple pathogens including potyviruses controlled by the I gene. Bean pod mottle virus (BPMV) is a comovirus that infects common bean and legumes in general. BPMV is distributed throughout the world and is a major threat on soybean, a closely related species of common bean. In common bean, BAT93 was reported to carry the R-BPMV resistance gene conferring resistance to BPMV and linked with the I resistance gene. To fine map R-BPMV, 182 recombinant inbred lines (RILs) derived from the cross BAT93 × JaloEEP558 were genotyped with polymerase chain reaction (PCR)-based markers developed using genome assemblies from G19833 and BAT93, as well as BAT93 BAC clone sequences. Analysis of RILs carrying key recombination events positioned R-BPMV to a target region containing at least 16 TIR-NB-LRR (TNL) sequences in BAT93. Because the I cluster presents a suppression of recombination and a large number of repeated sequences, none of the 16 TNLs could be excluded as R-BPMV candidate gene. The evolutionary history of the TNLs for the I cluster were reconstructed using microsynteny and phylogenetic analyses within the legume family. A single I TNL was present in Medicago truncatula and lost in soybean, mirroring the absence of complete BPMV resistance in soybean. Amplification of TNLs in the I cluster predates the divergence of the Phaseolus species, in agreement with the emergence of R-BPMV before the separation of the common bean wild centers of diversity. This analysis provides PCR-based markers useful in marker-assisted selection (MAS) and laid the foundation for cloning of R-BPMV resistance gene in order to transfer the resistance into soybean.
Subject(s)
Comovirus , Phaseolus , Phaseolus/genetics , Phylogeny , Genotype , Glycine max/geneticsABSTRACT
KEY MESSAGE: Quantitative Trait Loci "hotspots" for drought tolerance were identified on chromosomes Pv06, Pv07 and Pv10 of common bean. Drought is a major production constraint of common bean (Phaseolus vulgaris L.) worldwide. The objective of this study was to identify the Quantitative Trait Loci (QTL) for drought tolerance in an Andean population of Recombinant Inbred Lines (RILs). A total of 155 F5:7 RILs derived from a cross between Kijivu (drought tolerant) and Bukoba (drought susceptible) were evaluated for drought tolerance in field and pot experiments. Four field experiments were conducted at three locations in Zambia in 2020 and 2021. All field trials were conducted in the dry season under irrigation. The 155 RILs were genotyped with 11,292 SNPs, and composite interval mapping was conducted to identify QTL for drought tolerance. Seed yield for Kijivu under drought stress was consistently higher than for Bukoba across all four field trials. A total of 60 QTL were identified for morphological, agronomic, and physiological traits under drought stress and non-stress conditions. However, the majority of these QTL were specific to drought stress. QTL "hotspots" for drought tolerance were identified on chromosomes Pv06, Pv07, and Pv10. Extensive co-localizations for agronomic and morpho-physiological traits under drought stress were observed at the three drought-tolerance QTL hotspots. Additionally, these three QTL hotspots overlapped with previously identified QTL for drought tolerance, while several others identified QTL are novel. The three identified QTL hotspots could be used in future marker-assisted selection for drought tolerance in common bean.
Subject(s)
Phaseolus , Quantitative Trait Loci , Phaseolus/genetics , Chromosome Mapping , Drought Resistance , Phenotype , DroughtsABSTRACT
BACKGROUND: Common beans (Phaseolus vulgaris L.) provide important protein and calories globally. Anthracnose (Colletotrichum lindemuthianum (Sacc. & Magnus) Briosi & Cavara, 1889) is a major disease in common bean and causes significant yield losses in bean production areas. Screening for markers linked to known disease resistance genes provides useful information for plant breeders to develop improved common bean varieties. The Kompetitive Allele Specific PCR (KASP) assay is an affordable genetic screening technique that can be used to accelerate breeding programs, but manual DNA extraction and KASP assay preparation are time-consuming. Several KASP markers have been developed for genes involved in resistance to bean anthracnose, which can reduce yield by up to 100%, but their usefulness is hindered by the labor required to screen a significant number of bean lines. Our research objective was to develop publicly available protocols for DNA extraction and KASP assaying using a liquid handling robot (LHR) which would facilitate high-throughput genetic screening with less active human time required. Anthracnose resistance markers were used to compare manual and automated results. RESULTS: The 12 bean anthracnose differential cultivars were screened for four anthracnose KASP markers linked to the resistance genes Co-1, Co-3 and Co-42 both by hand and with the use of an LHR. A protocol was written for DNA extraction and KASP assay thermocycling to implement the LHR. The LHR protocol reduced the active human screening time of 24 samples from 3h44 to 1h23. KASP calls were consistent across replicates but not always accurate for their known linked resistance genes, suggesting more specific markers still need to be developed. Using an LHR, information from KASP assays can be accumulated with little active human time. CONCLUSION: Results suggest that LHRs can be used to expedite time-consuming and tedious lab work such as DNA extraction or PCR plate filling. Notably, LHRs can be used to prepare KASP assays for large sample sizes, facilitating higher throughput use of genetic marker screening tools.
ABSTRACT
White mold (WM), caused by the ubiquitous fungus Sclerotinia sclerotiorum, is a devastating disease that limits production and quality of dry bean globally. In the present study, classic linkage mapping combined with QTL-seq were employed in two recombinant inbred line (RIL) populations, "Montrose"/I9365-25 (M25) and "Raven"/I9365-31 (R31), with the initial goal of fine-mapping QTL WM5.4 and WM7.5 that condition WM resistance. The RILs were phenotyped for WM reactions under greenhouse (straw test) and field environments. The general region of WM5.4 and WM7.5 were reconfirmed with both mapping strategies within each population. Combining the results from both mapping strategies, WM5.4 was delimited to a 22.60-36.25 Mb interval in the heterochromatic regions on Pv05, while WM7.5 was narrowed to a 0.83 Mb (3.99-4.82 Mb) region on the Pv07 chromosome. Furthermore, additional QTL WM2.2a (3.81-7.24 Mb), WM2.2b (11.18-17.37 Mb, heterochromatic region), and WM2.2c (23.33-25.94 Mb) were mapped to a narrowed genomic interval on Pv02 and WM4.2 in a 0.89 Mb physical interval at the distal end of Pv04 chromosome. Gene models encoding gibberellin 2-oxidase proteins regulating plant architecture are likely candidate genes associated with WM2.2a resistance. Nine gene models encoding a disease resistance protein (quinone reductase family protein and ATWRKY69) found within the WM5.4 QTL interval are putative candidate genes. Clusters of 13 and 5 copies of gene models encoding cysteine-rich receptor-like kinase and receptor-like protein kinase-related family proteins, respectively, are potential candidate genes associated with WM7.5 resistance and most likely trigger physiological resistance to WM. Acquired knowledge of the narrowed major QTL intervals, flanking markers, and candidate genes provides promising opportunities to develop functional molecular markers to implement marker-assisted selection for WM resistant dry bean cultivars.
Subject(s)
Chromosomes, Plant , Quantitative Trait Loci , Chromosome Mapping/methods , Phenotype , Disease Resistance/geneticsABSTRACT
White mold (WM) is a major disease in common bean (Phaseolus vulgaris L.), and its complex quantitative genetic control limits the development of WM resistant cultivars. WM2.2, one of the nine meta-QTL with a major effect on WM tolerance, explains up to 35% of the phenotypic variation and was previously mapped to a large genomic interval on Pv02. Our objective was to narrow the interval of this QTL using combined approach of classic QTL mapping and QTL-based bulk segregant analysis (BSA), and confirming those results with Khufu de novo QTL-seq. The phenotypic and genotypic data from two RIL populations, 'Raven'/I9365-31 (R31) and 'AN-37'/PS02-029C-20 (Z0726-9), were used to select resistant and susceptible lines to generate subpopulations for bulk DNA sequencing. The QTL physical interval was determined by considering overlapping interval of the identified QTL or peak region in both populations by three independent QTL mapping analyses. Our findings revealed that meta-QTL WM2.2 consists of three regions, WM2.2a (4.27-5.76 Mb; euchromatic), WM 2.2b (12.19 to 17.61 Mb; heterochromatic), and WM2.2c (23.01-25.74 Mb; heterochromatic) found in both populations. Gene models encoding for gibberellin 2-oxidase 8, pentatricopeptide repeat, and heat-shock proteins are the likely candidate genes associated with WM2.2a resistance. A TIR-NBS-LRR class of disease resistance protein (Phvul.002G09200) and LRR domain containing family proteins are potential candidate genes associated with WM2.2b resistance. Nine gene models encoding disease resistance protein [pathogenesis-related thaumatin superfamily protein and disease resistance-responsive (dirigent-like protein) family protein etc] found within the WM2.2c QTL interval are putative candidate genes. WM2.2a region is most likely associated with avoidance mechanisms while WM2.2b and WM2.2c regions trigger physiological resistance based on putative candidate genes.
ABSTRACT
BACKGROUND: Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes. METHODS: We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort). FINDINGS: We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 [95% CI [0·78-0·89]) versus the fibrosis-4 index (FIB-4; 0·68 [0·61-0·75] at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347-641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88-0·91) versus 0.84 (0·82-0·86) for FIB-4. INTERPRETATION: The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care. FUNDING: European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).
Subject(s)
Liver Cirrhosis , Humans , Prognosis , Prospective Studies , Liver Cirrhosis/diagnosis , Liver Cirrhosis/epidemiology , Risk Factors , FibrosisABSTRACT
Beet curly top virus (BCTV), which is synonymous with curly top virus (CTV), causes significant yield loss in common bean (snap and dry beans) cultivars and several other important crops. Common bean cultivars have been found to be resistant to CTV, but screening for resistance is challenging due to the cyclical nature of epidemics and spotty feeding by the leafhopper that vectors the virus. We used an SNP dataset for the Snap Bean Association Panel (SnAP) agro-inoculated with CTV-Logan (CA/Logan) strain to locate the Bct gene region to a 1.7-Mb interval on chromosome Pv07 using genome-wide association study (GWAS) analysis. Recombinant lines from the SnAP were used to further narrow the Bct region to a 58.0-kb interval. A missense SNP (S07_2970381) in candidate gene Phvul.007G036300 Exonuclease V (EXO5) was identified as the most likely causal mutation, and it was the most significant SNP detected by GWAS in a dry bean population (DBP) naturally infected by the CTV-Worland (Wor) strain. Tm-shift assay markers developed for SNP S07_2970381 and two linked SNPs, S07_2970276 and S07_2966197, were useful for tracking different origins of the Bct EXO5 candidate gene resistance to CTV in common bean. The three SNPs identified four haplotypes, with haplotype 3-1 (Haplo3-1) of Middle American origin associated with the highest levels of CTV resistance. This SNP-haplotype assay will enable breeders to track resistance sources and to develop cultivars with better CTV resistance.
ABSTRACT
OBJECTIVE: The purpose of this integrative review was to explore, appraise and synthesize the current literature on correlates of suicide risk in nurses. DESIGN: Integrative literature review. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Joanna Briggs Institute, PubMed, PsycInfo and Scopus electronic databases were searched for abstracts published between 2005 and 2020. Reference lists were hand searched. REVIEW METHODS: The integrative review was based on the Whittemore and Knafl review methodology. Primary qualitative and quantitative studies about suicidal behaviour in nurses published in peer-reviewed journals were included. The methodological quality of included articles was assessed using the Mixed Methods Assessment Tool. RESULTS: Separate correlates of risk and protective factors were identified for suicidal ideation, suicide attempt and death by suicide in nurses. IMPLICATIONS: Due to a number of factors at the individual, interpersonal and work levels, nurses are uniquely positioned to be at risk of dying by suicide. The ideation-to-action framework provides a theoretical guide to understand the interplay between correlates and the effect it has on increasing a nurses' capability for suicide. CONCLUSIONS: This review integrates the empirical literature to elucidate the concept of suicidal behaviour as it applies to nurses.