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Cassava ( Manihot esculenta Crantz) is a vital carbohydrate source for over 800 million people globally, yet its production in East Africa is severely affected by cassava brown streak disease (CBSD). Genebanks, through ex-situ conservation, play a pivotal role in preserving crop diversity, providing crucial resources for breeding resilient and disease-resistant crops. This study genotyped 234 South American cassava accessions conserved at the CIAT genebank, previously phenotyped for CBSD resistance by an independent group, to perform a genome-wide association analysis (GWAS) to identify genetic variants associated with CBSD resistance. Our GWAS identified 35 single nucleotide polymorphism (SNP) markers distributed across various chromosomes, associated with disease severity or the presence/absence of viral infection. Markers were annotated within or near genes previously identified with functions related to pathogen recognition and immune response activation. Using the SNP candidates, we screened the world’s largest cassava collection for accessions with a higher frequency of favorable genotypes, proposing 35 accessions with potential resistance to CBSD. Our results provide insights into the genetics of CBSD resistance and highlight the importance of genetic resources to equip breeders with the raw materials needed to develop new crop varieties resistant to pests and diseases.

Crop diversity conserved in genebanks facilitates the development of superior varieties, improving yields, nutrition, adaptation to climate change and resilience against pests and diseases. Cassava ( Manihot esculenta ) plays a vital role in providing carbohydrates to approximately 500 million people in Africa and other continents. The International Center for Tropical Agriculture (CIAT) conserves the largest global cassava collection, housing 5,963 accessions of cultivated cassava and wild relatives within its genebank. Efficient genebank management requires identifying and eliminating genetic redundancy within collections. In this study, we optimized the identification of genetic redundancy in CIAT’s cassava genebank, applying empirical distance thresholds, and using two types of molecular markers (single-nucleotide polymorphism (SNP) and SilicoDArT) on 5,302 Manihot esculenta accessions. A series of quality filters were applied to select the most informative and high-quality markers and to exclude low-quality DNA samples. The analysis identified a total of 2,518 and 2,526 (47 percent) distinct genotypes represented by 1 to 87 accessions each, using SNP or SilicoDArT markers, respectively. A total of 2,776 (SNP) and 2,785 (SilicoDArT) accessions were part of accession clusters with up to 87 accessions. Comparing passport and historical characterization data, such as pulp color and leaf characteristic, we reviewed clusters of genetically redundant accessions. This study provides valuable guidance to genebank curators in defining minimum genetic-distance thresholds to assess redundancy within collections. It aids in identifying a subset of genetically distinct accessions, prioritizing collection management activities such as cryopreservation and provides insights for follow-up studies in the field, potentially leading to removal of duplicate accessions.

Abstract Context Levothyroxine is one of the most prescribed medications in the United States. Objective This study explores the appropriateness of levothyroxine prescriptions. Methods A retrospective multicenter study was conducted on adult patients who were prescribed levothyroxine for the first time between 2017 and 2020 at three academic centers in the United States. We classified each case of levothyroxine initiation into one of three mutually exclusive categories: appropriate (clinically supported), indeterminate (clinically unclear), or nonevidence based (NEB, not clinically supported). Results A total of 977 participants were included. The mean age was 55 years (SD 19), there was female (69%) and White race predominance (84%), and 44% had possible hypothyroid symptoms. Nearly half of the levothyroxine prescriptions were considered NEB (528, 54%), followed by appropriate (307, 31%) and indeterminate (118, 12%). The most common reason for NEB prescription was an index thyrotropin (TSH) value of less than 10 mIU/L without previous TSH or thyroxine values (131/528, 25%), for appropriate prescription, was overt hypothyroidism (163/307, 53%), and for an indeterminate prescription was a nonconfirmed subclinical hypothyroidism with TSH greater than or equal to 10 mIU/L (no confirmatory testing) (51/118, 43%). In multivariable analysis, being female (odds ratio [OR]: 1.3; 95% CI, 1.0-1.7) and prescription by a primary care provider (OR: 1.5; 95% CI, 1.2-2.0) were associated with NEB prescriptions. Conclusion There is a considerable proportion of NEB levothyroxine prescriptions. These results call for additional research to replicate these findings and to explore the perspective of those prescribing and receiving levothyroxine.

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration. Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

Open access to sequence data is a cornerstone of biology and biodiversity research, but has created tension under the United Nations Convention on Biological Diversity (CBD). Policy decisions could compromise research and development, unless a practical multilateral solution is implemented. Ensuring international benefit-sharing from sequence data without jeopardising open sharing is a major obstacle for the Convention on Biological Diversity and other UN negotiations. Here, the authors propose a solution to address the concerns of both developing countries and life scientists.

Genotyping large-scale gene bank collections requires an appropriate sampling strategy to represent the diversity within and between accessions. A panel of 44 common bean ( L.) landraces from the Alliance Bioversity and The Alliance of Bioversity International and the International Center for Tropical Agriculture (CIAT) gene bank was genotyped with DArTseq using three sampling strategies: a single plant per accession, 25 individual plants per accession jointly analyzed after genotyping ( ), and by pooling tissue from 25 individual plants per accession ( ). Sampling strategies were compared to assess the technical aspects of the samples, the marker information content, and the genetic composition of the panel. The strategy resulted in more consistent DNA libraries for quality and call rate, although with fewer polymorphic markers (6,142 single-nucleotide polymorphisms) than the (14,074) or the single plant sets (6,555). Estimates of allele frequencies by and genotyping were consistent, but the results suggest that the difference between pools depends on population heterogeneity. Principal coordinate analysis, hierarchical clustering, and the estimation of admixture coefficients derived from a single plant, - , and successfully identified the well-known structure of Andean and Mesoamerican gene pools of across all datasets. In conclusion, proved to be a viable approach for characterizing common bean germplasm compared to genotyping individual plants separately by balancing genotyping effort and costs. This study provides insights and serves as a valuable guide for gene bank researchers embarking on genotyping initiatives to characterize their collections. It aids curators in effectively managing the collections and facilitates marker-trait association studies, enabling the identification of candidate markers for key traits.

Paenibacillus larvae , the causative agent of American foulbrood (AFB), produces spores that may be detectable within honey. We analyzed the spore content of pooled, extracted honey from 52 large-scale (L) and 64 small-scale (S) Saskatchewan beekeepers over a two-year period (2019–2020). Our objectives were: (i) establish reliable prognostic reference ranges for spore concentrations in extracted honey to determine future AFB risk at the apiary level; (ii) identify management practices as targets for mitigation of risk. P. larvae spores were detected in 753 of 1476 samples (51%). Beekeepers were stratified into low (< 2 spores/gram), moderate (2- < 100 spores/gram), and high (≥ 100 spores/gram) risk categories. Of forty-nine L beekeepers sampled in 2019, those that reported AFB in 2020 included 0/26 low, 3/18 moderate, and 3/5 high risk. Of twenty-seven L beekeepers sampled in 2020, those that reported AFB in 2021 included 0/11 low, 2/14 moderate, and 1/2 high risk. Predictive modelling included indoor overwintering of hives, purchase of used equipment, movement of honey-producing colonies between apiaries, beekeeper demographic, and antimicrobial use as risk category predictors. Saskatchewan beekeepers with fewer than 2 spores/gram in extracted honey that avoid high risk activities may be considered at low risk of AFB the following year.

OBJECTIVES Extended septal myectomy and alcohol septal ablation are 2 invasive treatments for hypertrophic obstructive cardiomyopathy. Our goal was to compare which of these techniques achieved a higher reduction in gradients, improvement in New York Heart Association (NYHA) functional class and reduction in medical treatment. METHODS It is a single-centre observational and retrospective analysis. We used multivariable regression analyses to assess the association of ablation/myectomy with different outcomes. The odds ratio or coefficient along with the 95% confidence interval was estimated according to the group and adjusted for the corresponding preprocedural variables and EuroSCORE II. RESULTS A total of 78 patients underwent septal myectomy, and 25 patients underwent alcohol septal ablation. Basal and Valsalva gradients after myectomy were reduced to a higher degree in comparison to ablation: 21.0 mmHg [P < 0.001, 95% confidence interval -30.7; -11.3], and 34.3 mmHg (P < 0.001, -49.1; -19.5) respectively. Those patients who received a myectomy had a lower probability of having moderate mitral regurgitation (odds ratio = 0.18, P = 0.054). Patients after septal myectomy were more likely to be NYHA functional class I (80.4%), whereas patients after ablation were more likely to be NYHA functional class III (48%). Both groups continued with beta-blocker therapy, but disopyramide could be discontinued after the myectomy in more cases (20%–36% vs 59%–1.3%; P < 0.001), and there was a tendency to discontinue calcium channel blockers (48%–16% vs 15.4–3.8%; P = 0.054). CONCLUSIONS After adjustment using preprocedural gradients and EuroSCORE II, myectomy achieves greater reduction in left ventricular outflow tract gradients compared to septal ablation. Hypertrophic obstructive cardiomyopathy (HOCM) is a genetic and familiar disease with an incidence that oscillates between 0.2% and 0.5% [1–2]. Graphical Abstract

Among horses selected for speed, the racing line of Quarter Horses is characterized by high performance in sprint races, with these animals being considered the fastest horses in the world. However, few studies have investigated in more detail the polymorphisms and genes that act on this trait. The objective of this study was to analyze exomes and UTRs in regions previously associated with this trait by GWAS in Quarter Horse racehorses with contrasting maximum speed index (SImax), prospecting causal gene polymorphisms that are related to or are in strong linkage disequilibrium with racing performance. Genotypic and phenotypic records from 360 animals of the racing line of Quarter Horses, previously genotyped with an SNP chip to obtain individual genomic estimated breeding values for performance, were used for the formation and sequencing of two groups of animals with contrasting racing performance (20 animals with superior SImax and 20 with inferior SImax). Two rapid runs were performed using two pools of libraries containing 20 and 19 samples randomly chosen among the 40 samples with contrasting SIs. A total of 1203 variants (1105 SNPs and 93 InDels) were identified in 33 regions of interest obtained previously by GWAS. Twenty-nine of the polymorphisms (24 SNPs and 5 InDels) were considered to be important based on three different and independent approaches: SIFT scores classified as deleterious (< 0.05), degree of impact on the consensus region of each polymorphism, and different allele frequencies identified by Fisher’s exact test (p < 0.01) between the groups of horses with contrasting SImax. Thus, eight genes described as functional and positional candidates in previous studies (ABCG5, COL11A1, GEN1, SOCS3, MICAL1, SPTBN1, EPB41L3, and SHQ1) and nine new candidate genes (AKNA, ARMC2, FKBP15, LHX1, NOL10, TMEM192, ZFP37, FIG4, and HNRNPU), some of them with known function, were related to racing performance in Quarter Horses.