Genetic mapping of legume orthologs reveals high conservation of synteny between lentil species and the sequenced genomes of Medicago and chickpea.

Lentil (Lens culinaris Medik.) is a global food crop with increasing importance for food security in south Asia and other regions. Lens ervoides, a wild relative of cultivated lentil, is an important source of agronomic trait variation. Lens is a member of the galegoid clade of the Papilionoideae family, which includes other important dietary legumes such as chickpea (Cicer arietinum) and pea (Pisum sativum), and the sequenced model legume Medicago truncatula. Understanding the genetic structure of Lens spp. in relation to more fully sequenced legumes would allow leveraging of genomic resources. A set of 1107 TOG-based amplicons were identified in L. ervoides and a subset thereof used to design SNP markers for mapping. A map of L. ervoides consisting of 377 SNP markers spread across seven linkage groups was developed using a GoldenGate genotyping array and single SNP marker assays. Comparison with maps of M. truncatula and L. culinaris documented considerable shared synteny and led to the identification of a few major translocations and a major inversion that distinguish Lens from M. truncatula, as well as a translocation that distinguishes L. culinaris from L. ervoides. The identification of chromosome-level differences among Lens spp. will aid in the understanding of introgression of genes from L. ervoides into cultivated L. culinaris, furthering genetic research and breeding applications in lentil

Population studies of Ascochyta rabiei on chickpea in Saskatchewan

An epidemic increase in severity and incidence of asochyta blight, caused by Ascochyta rabiei (Pass) Labrousse (teleomorph: Didymella rabiei (Kovachevski) v. Arx. Syn. Mycosphaerella rabiei Kovachevski), has occurred on chickpea (Cicer arietinum L.) crops in Saskatchewan over the past 5 growing seasons. In order to explore the nature of the outbreak, studies assessing population differences in pathogenicity and genetic variability were employed. Isolates of A. rabiei collected in 1998, 2001 and 2002 were inoculated onto 7 differential chickpea genotypes for pathogenicity testing. Significant isolate by differential interaction occurred, but accounted for a low proportion of the total variability suggesting no genotype specific relationship exists between A. rabiei and C. arietinum. Furthermore, it was found that when averaged over all differentials, the isolates from 2001 and 2002 caused significantly greater disease than isolates from 1998, suggesting that the disease epidemic is in part due to a shift in the population to overall greater aggressiveness. The largest increase in disease severity was observed on the cultivar ‘Sanford’, which was widely grown in commercial chickpea fields before 1999. To evaluate the genetic diversity of different A. rabiei populations, 30 isolates from 1998 and 30 isolates from 2002 were compared with random amplified polymorphic DNA fingerprinting. Several clusters of isolates collected from either 1998 or 2002 were approximately 60% genetic similar suggesting divergence of these populations of A. rabiei. However, analysis of molecular variance showed that over 90% of the variation occurred within populations. Pairwise differences and gene diversity over loci showed that genetic diversity of the 2 populations had the same amount of genetic variability. Analysis of mating type distributions revealed that the populations from 1998, 2001 and 2002 did not significantly depart from a 1:1 ratio suggesting random mating of each population. Further supporting the hypothesis of a randomly mating population, linkage disequilibrium for both 1998 and 2002 populations was very low

Contrasting Nitrogen Fertilization and Brassica napus (Canola) Variety Development Impact Recruitment of the Root-Associated Microbiome

© 2023 The American Phytopathological SocietyPlant Phenotyping and Imaging Research Centre; the Canola Council of Canada, Alberta Canola, SaskCanola and Manitoba Canola Growers Association; and the Government of Canada under the Canadian Agricultural Partnership's AgriScience Program, a federal, provincial, territorial initiativePeer ReviewedCanola (Brassica napus) is an important broadacre crop, produced under high nitrogen (N) fertilizer application. Modern canola varieties are developed under high N rates but the impacts on root-associated microbiomes of different varieties are unknown. We studied eight canola varieties spanning historical Canadian spring canola development at two sites under high and low N fertility and characterized bacterial and fungal microbiomes in the root and rhizosphere using amplicon sequencing. Environmental conditions and the resulting canola varietal responses strongly affected the root-associated bacterial and fungal microbiomes. Microbes regulated by N fertility in each canola variety were mainly Gammaproteobacteria, Bacteroidia, Actinobacteria, Sordariomycetes, Dothideomycetes, and Agaricomycetes classes. Differentially abundant (DA) microbial taxa showed that N more strongly enriched bacteria in the roots and fungi in the rhizosphere. Each variety had its specific pattern of DA amplicon sequence variants (ASVs) responding to soil N availability, and the profile of DA-ASVs in paired canola varieties were also altered by soil N availability, especially bacteria in the rhizosphere. The yield was strongly associated with a subset of microbial taxa, mainly from Proteobacteria, Actinobacteriota, and Ascomycota. These variety-dependent responses to N and links to yield performance make the root-associated microbiome a promising target for improving the agronomic performance of canola by manipulating microorganisms tailored to soil fertility and plant genotype

In-Vivo Biodistribution and Safety of 99mTc-LLP2A-HYNIC in Canine Non-Hodgkin Lymphoma

Theranostic agents are critical for improving the diagnosis and treatment of non-Hodgkin Lymphoma (NHL). The peptidomimetic LLP2A is a novel peptide receptor radiotherapy candidate for treating NHL that expresses the activated α4β1 integrin. Tumor-bearing dogs are an excellent model of human NHL with similar clinical characteristics, behavior, and compressed clinical course. Canine in vivo imaging studies will provide valuable biodistribution and affinity information that reflects a diverse clinical population of lymphoma. This may also help to determine potential dose-limiting radiotoxicity to organs in human clinical trials. To validate this construct in a naturally occurring model of NHL, we performed in-vivo molecular targeted imaging and biodistribution in 3 normal dogs and 5 NHL bearing dogs. 99mTc-LLP2A-HYNIC-PEG and 99mTc-LLP2A-HYNIC were successfully synthesized and had very good labeling efficiency and radiochemical purity. 99mTc-LLP2A-HYNIC and 99mTc-LLP2A-HYNIC-PEG had biodistribution in keeping with their molecular size, with 99mTc-LLP2A-HYNIC-PEG remaining longer in the circulation, having higher tissue uptake, and having more activity in the liver compared to 99mTc-LLP2A-HYNIC. 99mTc-LLP2A-HYNIC was mainly eliminated through the kidneys with some residual activity. Radioactivity was reduced to near-background levels at 6 hours after injection. In NHL dogs, tumor showed moderately increased activity over background, with tumor activity in B-cell lymphoma dogs decreasing after chemotherapy. This compound is promising in the development of targeted drug-delivery radiopharmaceuticals and may contribute to translational work in people affected by non-Hodgkin lymphoma

Gene expression profiling identifies inflammation and angiogenesis as distinguishing features of canine hemangiosarcoma

<p>Abstract</p> <p>Background</p> <p>The etiology of hemangiosarcoma remains incompletely understood. Its common occurrence in dogs suggests predisposing factors favor its development in this species. These factors could represent a constellation of heritable characteristics that promote transformation events and/or facilitate the establishment of a microenvironment that is conducive for survival of malignant blood vessel-forming cells. The hypothesis for this study was that characteristic molecular features distinguish hemangiosarcoma from non-malignant endothelial cells, and that such features are informative for the etiology of this disease.</p> <p>Methods</p> <p>We first investigated mutations of VHL and Ras family genes that might drive hemangiosarcoma by sequencing tumor DNA and mRNA (cDNA). Protein expression was examined using immunostaining. Next, we evaluated genome-wide gene expression profiling using the Affymetrix Canine 2.0 platform as a global approach to test the hypothesis. Data were evaluated using routine bioinformatics and validation was done using quantitative real time RT-PCR.</p> <p>Results</p> <p>Each of 10 tumor and four non-tumor samples analyzed had wild type sequences for these genes. At the genome wide level, hemangiosarcoma cells clustered separately from non-malignant endothelial cells based on a robust signature that included genes involved in inflammation, angiogenesis, adhesion, invasion, metabolism, cell cycle, signaling, and patterning. This signature did not simply reflect a cancer-associated angiogenic phenotype, as it also distinguished hemangiosarcoma from non-endothelial, moderately to highly angiogenic bone marrow-derived tumors (lymphoma, leukemia, osteosarcoma).</p> <p>Conclusions</p> <p>The data show that inflammation and angiogenesis are important processes in the pathogenesis of vascular tumors, but a definitive ontogeny of the cells that give rise to these tumors remains to be established. The data do not yet distinguish whether functional or ontogenetic plasticity creates this phenotype, although they suggest that cells which give rise to hemangiosarcoma modulate their microenvironment to promote tumor growth and survival. We propose that the frequent occurrence of canine hemangiosarcoma in defined dog breeds, as well as its similarity to homologous tumors in humans, offers unique models to solve the dilemma of stem cell plasticity and whether angiogenic endothelial cells and hematopoietic cells originate from a single cell or from distinct progenitor cells.</p

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Contrasting Nitrogen Fertilization and Brassica napus (Canola) Variety Development Impact Recruitment of the Root-Associated Microbiome

Canola (Brassica napus) is an important broadacre crop, produced under high nitrogen (N) fertilizer application. Modern canola varieties are developed under high N rates but the impacts on root-associated microbiomes of different varieties are unknown. We studied eight canola varieties spanning historical Canadian spring canola development at two sites under high and low N fertility and characterized bacterial and fungal microbiomes in the root and rhizosphere using amplicon sequencing. Environmental conditions and the resulting canola varietal responses strongly affected the root-associated bacterial and fungal microbiomes. Microbes regulated by N fertility in each canola variety were mainly Gammaproteobacteria, Bacteroidia, Actinobacteria, Sordariomycetes, Dothideomycetes, and Agaricomycetes classes. Differentially abundant (DA) microbial taxa showed that N more strongly enriched bacteria in the roots and fungi in the rhizosphere. Each variety had its specific pattern of DA amplicon sequence variants (ASVs) responding to soil N availability, and the profile of DA-ASVs in paired canola varieties were also altered by soil N availability, especially bacteria in the rhizosphere. The yield was strongly associated with a subset of microbial taxa, mainly from Proteobacteria, Actinobacteriota, and Ascomycota. These variety-dependent responses to N and links to yield performance make the root-associated microbiome a promising target for improving the agronomic performance of canola by manipulating microorganisms tailored to soil fertility and plant genotype

The Heterogeneous State and Legal Pluralism in Mozambique

This article analyzes some of the most salient features of the state and the legal system in Mozambique. I propose the concept of the heterogeneous state to highlight the breakdown of the modern equation between the unity of the state, on the one hand, and the unity of its legal and administrative operation, on the other. The centrality of legal pluralism is analyzed in light of an empirical research focused on community courts and traditional authorities. I use the concept of legal hybridization with the purpose of showing the porosity of the boundaries of the different legal orders and cultures in Mozambique and the deep cross-fertilizations or cross-contaminations among them. Special attention is given to the multicultural plurality resulting from the interaction between modern law and traditional law, the latter conceived here as an alternative modernity