WAPO-A1 is the causal gene of the 7AL QTL for spikelet number per spike in wheat

Improving our understanding of the genes regulating grain yield can contribute to the development of more productive wheat varieties. Previously, a highly significant QTL affecting spikelet number per spike (SNS), grain number per spike (GNS) and grain yield was detected on chromosome arm 7AL in multiple genome-wide association studies. Using a high-resolution genetic map, we established that the A-genome homeolog of WHEAT ORTHOLOG OF APO1 (WAPO-A1) was a leading candidate gene for this QTL. Using mutants and transgenic plants, we demonstrate in this study that WAPO-A1 is the causal gene underpinning this QTL. Loss-of-function mutants wapo-A1 and wapo-B1 showed reduced SNS in tetraploid wheat, and the effect was exacerbated in wapo1 combining both mutations. By contrast, spikes of transgenic wheat plants carrying extra copies of WAPO-A1 driven by its native promoter had higher SNS, a more compact spike apical region and a smaller terminal spikelet than the wild type. Taken together, these results indicate that WAPO1 affects SNS by regulating the timing of terminal spikelet formation. Both transgenic and wapo1 mutant plants showed a wide range of floral abnormalities, indicating additional roles of WAPO1 on wheat floral development. Previously, we found three widespread haplotypes in the QTL region (H1, H2 and H3), each associated with particular WAPO-A1 alleles. Results from this and our previous study, show that the WAPO-A1 allele in the H1 haplotype (115-bp deletion in the promoter) is expressed at significantly lower levels in the developing spikes than the alleles in the H2 and H3 haplotypes, resulting in reduced SNS. Field experiments also showed that the H2 haplotype is associated with the strongest effects in increasing SNS and GNS (H2>H3>H1). The H2 haplotype is already present in most modern common wheat varieties but is rare in durum wheat, where it might be particularly useful to improve grain yield.

Disruption of OsPHD1, Encoding a UDP-Glucose Epimerase, Causes JA Accumulation and Enhanced Bacterial Blight Resistance in Rice

Lesion mimic mutants (LMMs) have been widely used in experiments in recent years for studying plant physiological mechanisms underlying programmed cell death (PCD) and defense responses. Here, we identified a lesion mimic mutant, lm212-1, which cloned the causal gene by a map-based cloning strategy, and verified this by complementation. The causal gene, OsPHD1, encodes a UDP-glucose epimerase (UGE), and the OsPHD1 was located in the chloroplast. OsPHD1 was constitutively expressed in all organs, with higher expression in leaves and other green tissues. lm212-1 exhibited decreased chlorophyll content, and the chloroplast structure was destroyed. Histochemistry results indicated that H2O2 is highly accumulated and cell death is occurred around the lesions in lm212-1. Compared to the wild type, expression levels of defense-related genes were up-regulated, and resistance to bacterial pathogens Xanthomonas oryzae pv. oryzae (Xoo) was enhanced, indicating that the defense response was activated in lm212-1, ROS production was induced by flg22, and chitin treatment also showed the same result. Jasmonic acid (JA) and methyl jasmonate (MeJA) increased, and the JA signaling pathways appeared to be disordered in lm212-1. Additionally, the overexpression lines showed the same phenotype as the wild type. Overall, our findings demonstrate that OsPHD1 is involved in the regulation of PCD and defense response in rice.

Mapping and Characterization of QTLs for Awn Morphology Using Crosses between “Double-Awn” Wheat 4045 and Awnless Wheat Zhiluowumai

Awns play important roles in seed dispersal, protection against predators, and photosynthesis. The characterization of genes related to the formation of awns helps understand the regulation mechanisms of awn development. In the present study, the “double-awn” wheat 4045, which features super-long lemma awns and long glume awns, and an awnless wheat line, Zhiluowumai, were used to investigate QTLs or genes involved in awn development. QTL analysis identified three loci—Qawn-1D, Qawn-5A, and Qawn-7B—using a population of 101 4045 × ZLWM F2 plants. Fine mapping with a total of 9018 progenies narrowed the mapping interval of Qawn-5A to an 809-kb region, which was consistent with the B1 locus, containing five genes on chromosome 5AL. Gene structure and expression analysis indicated that TraesCS5A02G542800 was the causal gene, which was subsequently verified by overexpression of TraesCS5A02G542800 in a “double-awn” wheat, Yangmai20. The retained “double-awn” phenotype of transgenic plants suggested that B1 represses the elongation but does not influence the emergence of the awns. Moreover, 4045 harbors a new allele of B1 with a 261-bp insertion in the promoter region and a lack of the EAR2 motif in the encoding region, which influences several important agronomic traits. In this study, we identify two novel QTLs and a novel allele of B1, providing new resources for exploration of awn development.

Could the candidate causal gene (LZTFL1) identified by Oxford University scientists, which doubles the risk of COVID-19-related respiratory failure, be used to boost the Weak immunogenicity of COVID-19 mRNA vaccines in patients with B-cell chronic lymphocytic leukemia (CLL)???. A double edged sward

Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of severe infections due to disease- and treatment-related immunodeficiency. As a result, patients with hematologic malignancies have been given priority for primary COVID-19 vaccination. Unfortunately, many studies have suggested that patients with B-cell chronic lymphocytic leukemia (CLL) who have been fully vaccinated can develop severe and often fatal complications. Therefore, adjuvants that can induce mRNA vaccine efficacy are desperately needed for this category of patients with haematological malignancies. A recent, study by Oxford University scientists showed that leucine zipper transcription factor-like 1(LZTFL1), as a candidate causal gene and its enhancer the rs17713054 A risk allele was significantly responsible for the twofold increased risk of respiratory failure from COVID-19 associated with 3p21.31.By using sequence analysis, the risk allele generates a second CCAAT/enhancer binding protein beta (CEBPB) motif in the enhancer. Moreover, neither LZTFL1 variants found in T cells nor B cells are responsible for increasing death risk from COVID-19 infection according to oxford study. Here, we propose attestable hypothesis that trans retinoic acid could enhance the immune response in vaccinated patients with B-cell chronic lymphocytic leukemia (CLL) according to the recent findings of Oxford scientists by inducing the casual gene(LZTFL1) in CD4 T cells and inhibiting (CEBPB) motif.

Comparative Analysis of Coding and Non-Coding Features within Insect Tolerance Loci in Wheat with Their Homologs in Cereal Genomes

Food insecurity and malnutrition have reached critical levels with increased human population, climate fluctuations, water shortage; therefore, higher-yielding crops are in the spotlight of numerous studies. Abiotic factors affect the yield of staple food crops; among all, wheat stem sawfly (Cephus cinctus Norton) and orange wheat blossom midge (Sitodiplosis mosellana) are two of the most economically and agronomically harmful insect pests which cause yield loss in cereals, especially in wheat in North America. There is no effective strategy for suppressing this pest damage yet, and only the plants with intrinsic tolerance mechanisms such as solid stem phenotypes for WSS and antixenosis and/or antibiosis mechanisms for OWBM can limit damage. A major QTL and a causal gene for WSS resistance were previously identified in wheat, and 3 major QTLs and a causal gene for OWBM resistance. Here, we present a comparative analysis of coding and non-coding features of these loci of wheat across important cereal crops, barley, rye, oat, and rice. This research paves the way for our cloning and editing of additional WSS and OWBM tolerance gene(s), proteins, and metabolites.

Cocaine-induced locomotor activation differs across six sets of inbred mouse substrains

Cocaine use disorders (CUD) are devastating for affected individuals and impose a significant burden on society, but there are currently no FDA-approved therapies. The development of novel and effective treatments has been hindered by substantial gaps in our knowledge about the etiology of these disorders. The risk for developing a CUD is influenced by genetics, the environment and complex interactions between the two. Identifying specific genes and environmental risk factors that increase CUD risk would provide an avenue for the development of novel treatments. Rodent models of addiction-relevant behaviors have been a valuable tool for studying the genetics of response to drugs of abuse. Traditional genetic mapping using genetically and phenotypically divergent inbred mice has been successful in identifying numerous chromosomal regions that influence addiction-relevant behaviors, but these strategies rarely result in identification of the causal gene or genetic variant. To overcome this challenge, reduced complexity crosses (RCC) between closely related inbred mouse substrains have been proposed as a method for rapidly identifying and validating functional variants. The RCC approach is dependent on identifying phenotypic differences between substrains. To date, however, the study of addiction-relevant behaviors has been limited to very few sets of substrains, mostly comprising the C57BL/6 lineage. The present study expands upon the current literature to assess cocaine-induced locomotor activation in 20 inbred mouse substrains representing six inbred strain lineages (A/J, BALB/c, FVB/N, C3H/He, DBA/2 and NOD) that were either bred in-house or supplied directly by a commercial vendor. To our knowledge, we are the first to identify significant differences in cocaine-induced locomotor response in several of these inbred substrains. The identification of substrain differences allows for the initiation of RCC populations to more rapidly identify specific genetic variants associated with acute cocaine response. The observation of behavioral profiles that differ between mice generated in-house and those that are vendor-supplied also presents an opportunity to investigate the influence of environmental factors on cocaine-induced locomotor activity.

PpMYB36 Encodes a MYB-Type Transcription Factor That Is Involved in Russet Skin Coloration in Pear (Pyrus pyrifolia)

Fruit color is one of the most important external qualities of pear (Pyrus pyrifolia) fruits. However, the mechanisms that control russet skin coloration in pear have not been well characterized. Here, we explored the molecular mechanisms that determine the russet skin trait in pear using the F1 population derived from a cross between russet skin (‘Niitaka’) and non-russet skin (‘Dangshansu’) cultivars. Pigment measurements indicated that the lignin content in the skin of the russet pear fruits was greater than that in the non-russet pear skin. Genetic analysis revealed that the phenotype of the russet skin pear is associated with an allele of the PpRus gene. Using bulked segregant analysis combined with the genome sequencing (BSA-seq), we identified two simple sequence repeat (SSR) marker loci linked with the russet-colored skin trait in pear. Linkage analysis showed that the PpRus locus maps to the scaffold NW_008988489.1: 53297-211921 on chromosome 8 in the pear genome. In the mapped region, the expression level of LOC103929640 was significantly increased in the russet skin pear and showed a correlation with the increase of lignin content during the ripening period. Genotyping results demonstrated that LOC103929640 encoding the transcription factor MYB36 is the causal gene for the russet skin trait in pear. Particularly, a W-box insertion at the PpMYB36 promoter of russet skin pears is essential for PpMYB36-mediated regulation of lignin accumulation and russet coloration in pear. Overall, these results show that PpMYB36 is involved in the regulation of russet skin trait in pear.

Mining hidden knowledge: Embedding models of cause-effect relationships curated from the biomedical literature

We explore the use of literature-curated signed causal gene expression and gene-function relationships to construct un-supervised embeddings of genes, biological functions, and diseases. Our goal is to prioritize and predict activating and inhibiting functional associations of genes, and to discover hidden relationships between functions. As an application, we are particularly interested in the automatic construction of networks that capture relevant biology in a given disease context. We evaluated several unsupervised gene embedding models leveraging literature-curated signed causal gene expression findings. Using linear regression, it is shown that, based on these gene embeddings, gene-function relationships can be predicted with about 95% precision for the highest scoring genes. Func- tion embedding vectors, derived from parameters of the linear regression model, allow to infer relationships between different functions or diseases. We show for several diseases that gene and function embeddings can be used to recover key drivers of pathogenesis, as well as underlying cellular and physiological processes. These results are presented as disease-centric net- works of genes and functions. To illustrate the applicability of the computed gene and function embeddings to other machine learning tasks we expanded the embedding approach to drug molecules, and used a simple neural network to predict drug- disease associations.

All-Flesh Tomato Regulated by Reduced Expression Dosage of AFF Through a Promoter SV Mutation

The formation of locule gel is an important process in tomato and a typical characteristic of berry fruit. In this study, we collected a tomato natural mutant that produces all-flesh fruits (AFF) in which the locule tissue remains in a solid state during fruit development. We built genetic populations to fine-map the causal gene of the AFF trait and identified the gene AFF (SlMBP3) as the locus conferring the locule gel formation. We determined the causal mutation as a 416-bp deletion that occurred in the promoter region of AFF and reduced its expression dosage. The 416-bp sequence is highly conserved among Solanaceae species, as well as within the tomato germplasm. Furthermore, with the BC6 NIL materials, we revealed that the reduced expression dosage of AFF did not impact the normal development of seeds but produced unique non-liquefied locule tissue, which was distinct from that of normal tomatoes in terms of metabolic components. We further revealed the importance of AFF gene in locule tissue liquefaction through combined analysis using mRNA-seq and metabolomics. Our findings provide clues to investigate fruit type differentiation in Solanaceae crops and also contribute to the application of the AFF gene in tomato breeding programs.