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PeerJ 2024Wheat stem rust, which is caused by f. sp. (), is a highly destructive disease that affects wheat crops on a global scale. In this study, the reactions of 150 bread...
Wheat stem rust, which is caused by f. sp. (), is a highly destructive disease that affects wheat crops on a global scale. In this study, the reactions of 150 bread wheat varieties were evaluated for natural infection at the adult-plant stage in the 2019-2020 and 2020-2021 growing seasons, and they were analyzed using specific molecular markers to detect stem rust resistance genes (, , , , , , , and ). Based on phenotypic data, the majority of the varieties (62%) were resistant or moderately resistant to natural infection. According to molecular results, it was identified that was present in 103 varieties, in nine varieties, in six varieties, and , , and in one variety each. Additionally, their combinations + , + , + , and + were detected in these varieties. On the other hand, and were not identified. In addition, many varieties had low stem rust scores, including a large minority that lacked . These varieties must have useful resistance to stem rust and could be the basis for selecting greater, possibly durable resistance.
Topics: Triticum; Plant Diseases; Disease Resistance; Puccinia; Genetic Variation; Plant Stems; Genes, Plant; Basidiomycota
PubMed: 38948208
DOI: 10.7717/peerj.17633 -
PeerJ 2024Combining ability status of the inbred lines is crucial information for hybrid breeding program. Diallel or line × tester mating designs are frequently used to evaluate...
Combining ability status of the inbred lines is crucial information for hybrid breeding program. Diallel or line × tester mating designs are frequently used to evaluate the combining ability. In the current study a modified diallel model was used, wherein the Griffing's combining ability effects were further partitioned to understand the effects due to maternal and reciprocal. To do this, eight parental lines of maize were crossed in full diallel method and the generated hybrids along with parents were phenotyped. The field data on the quantitative traits was analyzed using both Griffing's and the modified model to determine how well the parents' and the F hybrids combined. For each of the traits, a sizable reciprocal and maternal variance was observed. The number of kernel rows per cob variable had a ratio of additive variance to dominance variance greater than one. All other traits including grain yield had a ratio close to zero, suggesting that non-additive gene action was primarily responsible for the genetic control of most of the traits. The narrow sense heritability was low to moderate for majority of the variables, except for number of kernel rows per cob. With the help of the improved model, it was possible to choose superior parents and cross-parent pairings with accuracy. Based on the modified general combining ability effects and maternal effects, the parental line P5 was recognized as a potential female parent and P7 as a good male parent for grain yield and yield-attributing characteristics. The cross combination of P8×P1 had the highest specific combining ability effect on grain yield. P5×P6 cross had the highest reciprocal effect. The correlation analysis implies that the Griffing's general combining ability effects and specific combining ability effects were found to be less efficient in predicting F performance as compared to the modified model.
Topics: Zea mays; Plant Breeding; Phenotype; Models, Genetic; Maternal Inheritance; Hybridization, Genetic
PubMed: 38948201
DOI: 10.7717/peerj.17600 -
Theranostics 2024: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the...
: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. : The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. : Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. : The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.
Topics: Animals; Disease Models, Animal; Mice; Mitochondria; YAP-Signaling Proteins; Signal Transduction; Hippo Signaling Pathway; Basolateral Nuclear Complex; Protein Serine-Threonine Kinases; Male; Stress, Psychological; 14-3-3 Proteins; Adaptor Proteins, Signal Transducing; Depressive Disorder, Major; Depression; Mice, Inbred C57BL; Neurons; Mice, Transgenic
PubMed: 38948066
DOI: 10.7150/thno.92676 -
Theranostics 2024Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung...
Myofibroblasts (MYFs) are generally considered the principal culprits in excessive extracellular matrix deposition and scar formation in the pathogenesis of lung fibrosis. Lipofibroblasts (LIFs), on the other hand, are defined by their lipid-storing capacity and are predominantly found in the alveolar regions of the lung. They have been proposed to play a protective role in lung fibrosis. We previously reported that a LIF to MYF reversible differentiation switch occurred during fibrosis formation and resolution. In this study, we tested whether WI-38 cells, a human embryonic lung fibroblast cell line, could be used to study fibroblast differentiation towards the LIF or MYF phenotype and whether this could be relevant for idiopathic pulmonary fibrosis (IPF). Using WI-38 cells, Fibroblast (FIB) to MYF differentiation was triggered using TGF-β1 treatment and FIB to LIF differentiation using Metformin treatment. We also analyzed the MYF to LIF and LIF to MYF differentiation by pre-treating the WI-38 cells with TGF-β1 or Metformin respectively. We used IF, qPCR and bulk RNA-Seq to analyze the phenotypic and transcriptomic changes in the cells. We correlated our transcriptome data from WI-38 cells (obtained via bulk RNA sequencing) with the transcriptomic signature of LIFs and MYFs derived from the IPF cell atlas as well as with our own single-cell transcriptomic data from IPF patients-derived lung fibroblasts (LF-IPF) cultured . We also carried out alveolosphere assays to evaluate the ability of the proposed LIF and MYF cells to support the growth of alveolar epithelial type 2 cells. : WI-38 cells and LF-IPF display similar phenotypical and gene expression responses to TGF-β1 and Metformin treatment. Bulk RNA-Seq analysis of WI-38 cells and LF-IPF treated with TGF-β1, or Metformin indicate similar transcriptomic changes. We also show the partial conservation of the LIF and MYF signature extracted from the Habermann scRNA-seq dataset in WI-38 cells treated with Metformin or TGF-β1, respectively. Alveolosphere assays indicate that LIFs enhance organoid growth, while MYFs inhibit organoid growth. Finally, we provide evidence supporting the MYF to LIF and LIF to MYF reversible switch using WI-38 cells. WI-38 cells represent a versatile and reliable model to study the intricate dynamics of fibroblast differentiation towards the MYF or LIF phenotype associated with lung fibrosis formation and resolution, providing valuable insights to drive future research.
Topics: Humans; Myofibroblasts; Cell Differentiation; Fibroblasts; Cell Line; Idiopathic Pulmonary Fibrosis; Transforming Growth Factor beta1; Lung; Transcriptome; Metformin; Cell Plasticity; Phenotype
PubMed: 38948058
DOI: 10.7150/thno.93519 -
Theranostics 2024The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between...
The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Here, an injectable H-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold to provide mechanical support. With the appropriate release of H and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Overall, our study provides critical insight into the design and development of H-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.
Topics: Animals; Magnesium; Reactive Oxygen Species; Mice; Polyethylene Glycols; Hydrogels; Osteoporosis; Osteogenesis; Hydrogen; RAW 264.7 Cells; Bone Regeneration; Immunomodulation; Tissue Scaffolds; Macrophages; Polyesters
PubMed: 38948054
DOI: 10.7150/thno.97412 -
World Journal of Clinical Pediatrics Jun 2024Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic... (Review)
Review
Over the past 20 years, the incidence and prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents have increased, particularly in racial and ethnic minorities. Despite the rise in T2DM in children and adolescents, the pathophysiology and progression of disease in this population are not clearly understood. Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM. Furthermore, the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients, mostly due to the challenges of implementing clinical trials. A better understanding of the mechanisms underlying the de-velopment and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies. This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.
PubMed: 38947996
DOI: 10.5409/wjcp.v13.i2.91587 -
Frontiers in Oncology 2024Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods...
INTRODUCTION
Type 2 diabetes mellitus (T2DM) was associated with digestive system tumors. We analyzed publicly available data from GWAS studies using Mendelian randomization methods to clarify its causal relationship and mechanisms. Five common digestive system tumors and four diabetes-related phenotypes were included.
METHODS
Inverse variance weighted method was the main analytical method. Meta-analysis was used to summarize results of multiple data sources. Horizontal pleiotropy was tested using Egger-intercept method and validated by MRPRESSO method. Heterogeneity and sensitivity analysis were conducted by Cochran's Q test and leave-one-out method, respectively.
RESULTS
T2DM is associated with a reduced risk of esophageal (OR: 0.77, 95% CI: 0.71 to 0.83, P< 0.001), gastric (OR: 0.87, 95% CI: 0.84 to 0.90, P< 0.001) and colorectal cancer (OR: 0.88, 95% CI: 0.85 to 0.91, P< 0.001) and hepatocellular carcinoma (OR: 0.92, 95% CI: 0.86 to 0.97, P = 0.005) and an increased risk of pancreatic cancer (OR: 1.92, 95% CI: 1.47 to 2.50, P< 0.001) in East Asian population. T2DM causes decreased fasting insulin levels (OR = 0.966, 95% CI: 0.95 to 0.98, P< 0.001) and increased glycated hemoglobin levels (OR=1.41, 95% CI: 1.39 to 1.44, P<0.001). Elevated fasting insulin levels increase the risk of esophageal cancer (OR = 10.35, 95% CI: 1.10 to 97.25, P = 0.041), while increased glycated hemoglobin levels increase pancreatic cancer risk (OR=2.33, 95% CI: 1.37 to 3.97, P=0.002) but decrease gastric cancer risk (OR=0.801, 95% CI: 0.65 to 0.99, P=0.044).
CONCLUSION
T2DM is associated with a reduced risk of esophageal, gastric and colorectal cancer and hepatocellular carcinoma in East Asian populations. The causal relationships between T2DM with esophageal and gastric cancer are partially mediated by decreased fasting insulin and increased glycated hemoglobin levels, respectively. T2DM indirectly increases the risk of pancreatic cancer by increasing glycated hemoglobin levels.
PubMed: 38947888
DOI: 10.3389/fonc.2024.1327154 -
Frontiers in Oncology 2024Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite the progress in HB treatment, investigating HB pathomechanisms to optimize stratification...
BACKGROUND
Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite the progress in HB treatment, investigating HB pathomechanisms to optimize stratification and therapies remains a focal point to improve the outcome for high-risk patients.
METHODS
Here, we pointed to explore the impact of these mechanisms in HB. An observational study was performed on liver samples from a cohort of 17 patients with a diagnosis of HB and two normal liver samples. The experiments were executed on the Huh6 human HB cell line treated with the FAK inhibitor TAE226.
RESULTS
Our results highlight a significant up-regulation of mRNA and protein expression of FAK in livers from HB with respect to normal livers. The increased protein expression of total and Tyr397 phosphorylated FAK (pTyr397FAK) was significantly correlated with the expression of some epigenetic regulators of histone H3 methylation and acetylation. Of note, the expression of pTyr397FAK, N-methyltransferase enzyme (EZH2) and tri-methylation of the H3K27 residue correlated with tumor size and alpha-fetoprotein (AFP) levels. Finally, TAE226 caused a significant reduction of pTyr397FAK, epigenetic regulators, , , , and , in association with anti-proliferative and pro-apoptotic effects on HB cells.
CONCLUSION
Our results suggest a role of FAK in HB that requires further investigations mainly focused on the exploration of its effective diagnostic and therapeutic translatability.
PubMed: 38947885
DOI: 10.3389/fonc.2024.1397647 -
IScience Jun 2024Comparisons of molecular phenotypes across primates provide unique information to understand human biology and evolution, and single-cell RNA-seq CRISPR interference...
Comparisons of molecular phenotypes across primates provide unique information to understand human biology and evolution, and single-cell RNA-seq CRISPR interference (CRISPRi) screens are a powerful approach to analyze them. Here, we generate and validate three human, three gorilla, and two cynomolgus iPS cell lines that carry a dox-inducible KRAB-dCas9 construct at the AAVS1 locus. We show that despite variable expression levels of KRAB-dCas9 among lines, comparable downregulation of target genes and comparable phenotypic effects are observed in a single-cell RNA-seq CRISPRi screen. Hence, we provide valuable resources for performing and further extending CRISPRi in human and non-human primates.
PubMed: 38947524
DOI: 10.1016/j.isci.2024.110090 -
IScience Jun 2024Evading host innate immune defenses is a critical feature of infections, and the mechanisms used by to subvert these pathways are incompletely understood. We screened...
Evading host innate immune defenses is a critical feature of infections, and the mechanisms used by to subvert these pathways are incompletely understood. We screened a library of chimeric mutants for genetic factors important for interference with cell-autonomous immune defenses. Mutant strains with predicted truncations of the inclusion membrane protein CT135 were susceptible to interferon gamma-activated immunity in human cells. CT135 functions to prevent host-driven recruitment of ubiquitin and p62/SQSTM to the inclusion membrane. In a nonhuman primate model of infection, a CT135-deficient strain was rapidly cleared, highlighting the importance of this virulence factor for pathogenesis. Analysis of CT135 phenotypes in primary macaque cells revealed that cell-autonomous immune defenses against are conserved between humans and nonhuman primates and connects mechanistic findings with infection outcomes.
PubMed: 38947519
DOI: 10.1016/j.isci.2024.110143