Cyclanilide Induces Lateral Bud Outgrowth by Modulating Cytokinin Biosynthesis and Signalling Pathways in Apple Identified via Transcriptome Analysis

Cyclanilide (CYC), a plant growth regulator, is a potent shoot branching agent in apple. However, its mechanism remains unclear. The current study revealed that CYC treatment resulted in massive reprogramming of the axillary bud transcriptome, implicating several hormones in the response. We observed a marked increase (approximately 2-fold) in the level of zeatin riboside and a significant decrease (approximately 2-fold) in the level of abscisic acid (ABA). Zeatin metabolism gene cytokinin (CTK) oxidase 1 (CKX 1) was down-regulated at 168 h after CYC treatment compared with the control. Weighted gene co-expression network analysis of differentially expressed genes demonstrated the turquoise module clusters exhibited the highest positive correlation with zeatin riboside (r = 0.92) and the highest negative correlation with ABA (r = −0.8). A total of 37 genes were significantly enriched in the plant hormone signal transduction pathway in the turquoise module. Among them, the expressions of CTK receptor genes WOODEN LEG and the CTK type-A response regulators genes ARR3 and ARR9 were up-regulated. ABA signal response genes protein phosphatase 2C genes ABI2 and ABI5 were down-regulated in lateral buds after CYC treatment at 168 h. In addition, exogenous application of 6-benzylaminopurine (6-BA, a synthetic type of CTK) and CYC enhanced the inducing effect of CYC, whereas exogenous application of lovastatin (a synthetic type of inhibitor of CTK biosynthesis) or ABA and CYC weakened the promoting effect of CYC. These results collectively revealed that the stimulation of bud growth by CYC might involve CTK biosynthesis and signalling, including genes CKX1 and ARR3/9, which provided a direction for further study of the branching promoting mechanism of CYC.

Polymorphism of methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene and hyperhomocysteinemia in migraine

В обзоре обсуждается роль полиморфизма гена фолатного обмена метилентетрагидрофолат-редуктазы (MTHFR), ответственного за развитие гипергомоцистеинемии в патогенезе мигрени. Изложены общие данные о полиморфизме С677 гена фолатного цикла и метаболизме гомоцистеина. Представлен патогенетический механизм развития мигрени, связанный с провоспалительными, прокоагулянтными свойствами гомоцистеина, активацией процессов окислительного стресса, эндотелиальной дисфункцией и нейрогенным воспалением при повышении концентрации этой аминокислоты. Отражены перспективы и социальная значимость имплементации данных генетических исследований в клиническую практику, их роль в прогнозировании течения мигрени и оценке риска развития осложнений, а также коррекции фармакотерапевтических подходов. Методика. Для поиска данных в базах MEDLINE, SCOPUS и Web of Science использованы поисковые запросы: МТHFR, мигрень, патофизиология, гипергомоцистеинемия, таргетная терапия. The review discusses the role of polymorphism of the methylenetetrahydrofolate reductase (MTHFR) folate metabolism gene responsible for hyperhomocysteinemia in the pathogenesis of migraine. Data on the polymorphism of the folate cycle gene C677 and homocysteine metabolism are presented. The pathogenetic mechanism of migraine associated with proinflammatory, procoagulant properties of homocysteine and with the activation of oxidative stress, endothelial dysfunction, and neurogenic inflammation related with increased concentrations of homocysteine is described. Prospects and social significance of implementing data of genetic research into clinical practice are discussed. Included is the role of genetic research in predicting the course and complications of migraine, in assessment of risk for complications, and in pharmacotherapeutic approaches to migraine treatment. Methods. MEDLINE, SCOPUS and Web of Science databases were used to search for data: MTHFR, migraine, pathophysiology, hyperhomocysteinemia, targeted therapy

Genomic analysis of Elsinoë arachidis reveals its potential pathogenic mechanism and the biosynthesis pathway of elsinochrome toxin

Elsinochromes (ESCs) are virulence factors produced by Elsinoë arachidis which is the cause of peanut scab. However, the biosynthesis pathway of ESCs in E. arachidis has not been elucidated and the potential pathogenic mechanism of E. arachidis is poorly understood. In this study, we report a high-quality genome sequence of E. arachidis. The size of the E. arachidis genome is 33.18Mb, which is comparable to the Ascomycota genome (average 36.91 Mb), encoding 9174 predicted genes. The self-detoxification family including transporters and cytochrome P450 enzymes were analysis, candidate effectors and cell wall degrading enzymes were investigated as the pathogenicity genes by using PHI and CAZy databases. Additionally, the E. arachidis genome contains 24 secondary metabolism gene clusters, in which ESCB1 was identified as the core gene of ESC biosynthesis. Taken together, the genome sequence of E. arachidis provides a new route to explore its potential pathogenic mechanism and the biosynthesis pathway of ESCs.

New Kendomycin Derivative Isolated from Streptomyces sp. Cl 58-27

In the course of screening new streptomycete strains, the strain Streptomyces sp. Cl 58-27 caught our attention due to its interesting secondary metabolite production profile. Here, we report the isolation and characterization of an ansamycin natural product that belongs structurally to the already known kendomycins. The structure of the new kendomycin E was elucidated using NMR spectroscopy, and the corresponding biosynthetic gene cluster was identified by sequencing the genome of Streptomyces sp. Cl 58-27 and conducting a detailed analysis of secondary metabolism gene clusters using bioinformatic tools.

Targeting Metabolic Dysregulation for Ruxolitinib Failure in MPN

Background:Metabolic alterations are increasingly recognized as an important pathogenic process that underlies fibrosis and cancer cells. MPN models were demonstrated to exhibit metabolic vulnerabilities due to a high dependence on enhanced levels of glycolysis and oxidative phosphorylation. MPN patients often gain weight during ruxolitinib treatment effects on leptin signaling. Ruxolitinib provides symptomatic relief and can improve survival but generally fails to resolve the malignant clone,nealy 50% patients resistance to ruxolitinib.Here,we will study transcriptomic and metabolomic program in JAK2-mutant MPN who resistance to ruxolitinib. Methods:The collection of blood samples and clinical data from MPN patients, Mice used in this study were kept in accordance with Swiss federal regulations. Multi-omics detection by transcriptome sequencing and liquid chromatography . Results: We found that active lipid metabolism obviously in patients resistance to ruxolitinib in comparison with patients sensitive to ruxolitinib.Transcriptomic and metabolomic analyses identified numerous metabolic nodes in JAK2-mutant hematopoietic stem and progenitor cells that were altered in comparison with wild-type controls. We studied the consequences of key regulatory enzyme of Fatty acid metabolism gene(SREBP,FASN, ACC, SCD1) and found that pharmacological inhibition of SREBP(Betulin) reduced hematopoietic manifestations of MPNs. Conclusion: Our findings reveal the contribution of metabolic alterations to JAK2 inhibitor failure and suggest that abnormally active lipid metabolism of mutant cells represent vulnerabilities that can be targeted for treating MPNs. Keywords: metabolomic;resistance;resistance;Myeloproliferative Disclosures No relevant conflicts of interest to declare.

Genome-wide identification and characteristic analysis of the downstream melatonin metabolism gene GhM2H in Gossypium hirsutum L.

Background Melatonin 2-hydroxylase (M2H) is the first enzyme in the catabolism pathway of melatonin, which catalyzes the production of 2-hydroxymelatonin (2-OHM) from melatonin. The content of 2-hydroxymelatonin in plants is much higher than that of melatonin. So M2H may be a key enzyme in the metabolic pathway of melatonin. Method We conducted a systematic analysis of the M2H gene family in Gossypium hirsutum based on the whole genome sequence by integrating the structural characteristics, phylogenetic relationships, expression profile, and biological stress of the members of the Gossypium hirsutum M2H gene family. Result We identified 265 M2H genes in the whole genome of Gossypium hirsutum, which were divided into 7 clades (clades I-VII) according to phylogenetic analysis. Most M2H members in each group had similar motif composition and gene structure characteristics. More than half of GhM2H members contain ABA-responsive elements and MeJA-responsive elements. Under different stress conditions, the expression levels of the gene changed, indicating that GhM2H members were involved in the regulation of abiotic stress. Some genes in the GhM2H family were involved in regulating melatonin levels in cotton under salt stress, and some genes were regulated by exogenous melatonin. Conclusion This study is helpful to explore the function of GhM2H, the downstream metabolism gene of melatonin in cotton, and lay the foundation for better exploring the molecular mechanism of melatonin improving cotton's response to abiotic stress.

Genic microsatellite marker characterization and development in little millet (Panicum sumatrense) using transcriptome sequencing

Little millet is a climate-resilient and high-nutrient value plant. The lack of molecular markers severely limits the adoption of modern genomic approaches in millet breeding studies. Here the transcriptome of three samples were sequenced. A total of 4443 genic-SSR motifs were identified in 30,220 unigene sequences. SSRs were found at a rate of 12.25 percent, with an average of one SSR locus per 10 kb. Among different repeat motifs, tri-nucleotide repeat (66.67) was the most abundant one, followed by di- (27.39P), and tetra- (3.83P) repeats. CDS contained fewer motifs with the majority of tri-nucleotides, while 3′ and 5′ UTR carry more motifs but have shorter repeats. Functional annotation of unigenes containing microsatellites, revealed that most of them were linked to metabolism, gene expression regulation, and response to environmental stresses. Fifty primers were randomly chosen and validated in five little millet and 20 minor millet genotypes; 48% showed polymorphism, with a high transferability (70%) rate. Identified microsatellites can be a noteworthy resource for future research into QTL-based breeding, genetic resource conservation, MAS selection, and evolutionary genetics.

Inflammation and metabolism gene sets in subcutaneous abdominal adipose tissue are altered 1 hour after exercise in adults with obesity

Although the health benefits of exercise in adults with obesity are well described, the direct effects of exercise on adipose tissue that may lead to improved metabolic health are poorly understood. The primary aims of this study were to perform an unbiased analysis of the subcutaneous abdominal adipose tissue transcriptomic response to acute exercise in adults with obesity, and to compare the effects of moderate-intensity continuous exercise vs. high-intensity interval exercise on this response. Twenty-nine adults with obesity performed a session of either high-intensity interval exercise (HI; 10x1 min at 90 %HRpeak, 1min recovery between intervals; n=14) or moderate-intensity continuous exercise (MI; 45 min at 70 %HRpeak; n=15). Groups were well-matched for BMI (HI 33±3 vs. MI 33±4 kg/m2), sex (HI: 9 women vs. MI: 10 women), and age (HI: 32±6 vs. MI: 29±5). Subcutaneous adipose tissue was collected before and 1 hour after the session of HI or MI, and samples were processed for RNA sequencing. Gene Set Enrichment Analysis revealed 7 of 21 gene sets enriched post-exercise overlapped between HI and MI. Interestingly, both HI and MI upregulated gene sets involved in inflammation (IL6-JAK-STAT3 signaling, allograft rejection, TNFA signaling via NFKB, and inflammatory response; FDR q-value<0.25). Exercise also downregulated adipogenic and oxidative metabolism gene sets in both groups. Overall, these data suggest genes involved in subcutaneous adipose tissue metabolism and inflammation may be an important part of the initial response after a session of exercise.