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At least 739 records · Page 41Linked to original sources
PubMed2026

Genome-wide identification and characterization of 1-amino-cyclopropane-1- carboxylate synthase (ACS) gene family in Carica papaya and expression insights in response to hormone stress.

ACC-synthase (1-aminocyclopropane-1-carboxylate synthase), also known as the ACS gene, plays a pivotal role in ethylene production, which is of great importance in the fruit ripening process for producing saleable yield (marketable fruit). The ACS gene family presumably controls stress responses, plant growth and development, and particularly fruit ripening. Computational biology was used as an essential tool to identify seven ACS genes in Carica papaya (red hermaphrodite) using an RNA-seq database (NCBI GEO). Further, the phylogenetic relationships of ACS genes determined gene family resemblance in the genomes of Hordeum vulgare, Musa acuminata, C. papaya, and Arabidopsis thaliana; therefore, the identified gene families were further classified into four distinct clades (Type-I, Type-II, Type-III, and Type-IV) in alignment with the well-established Arabidopsis classification. Moreover, encompassing gene structure, domain motifs, cis-element phylogenetic profiling, synteny, and transcriptomic profiling unveiled latent structural and functional attributes within CpACS genes. Through segmental duplication of CpACS, insights into evolutionary duplication events were predicted. The paralogous behavior of ACS genes in C. papaya and a comprehensive transcriptomic analysis demonstrated both up- and down-regulation patterns in response to ethylene treatment at different time points during the fruit ripening process, using the papaya manual handbook V2 (2021). Gene expression showed upregulation of two essential CpACS genes, CpACS5 and CpACS6. RT-qPCR validates the expression of these important genes during fruit ripening. However, one gene, CpACS7, is expressed in the later stages of fruit development. Our results demonstrated novel avenues for understanding the expression pathways of the ACS gene family in red hermaphrodite papaya, and most of these genes were linked to regulating various abiotic stresses, plant growth, and fruit development.

Carica↗
PubMed2025

Gfa1 (glutamine fructose-6-phosphate aminotransferase) is essential for Aspergillus fumigatus growth and virulence.

BACKGROUND: Aspergillus fumigatus, the primary etiological agent of invasive aspergillosis, causes over 1.8 million deaths annually. Targeting cell wall biosynthetic pathways offers a promising antifungal strategy. Gfa1, a rate-limiting enzyme in UDP-GlcNAc synthesis, plays a pivotal role in the hexosamine biosynthetic pathway (HBP). RESULTS: Deletion of gfa1 (Δgfa1) results in auxotrophy for glucosamine (GlcN) or N-acetylglucosamine (GlcNAc). Under full recovery (FR) conditions, where minimal medium is supplemented with 5 mM GlcN as the sole carbon source, the Δgfa1 mutant shows growth comparable to the wild-type (WT). However, when supplemented with 5 mM GlcN and 55 mM glucose, growth is partially repressed, likely due to carbon catabolite repression, a condition termed partial repression (PR). Under PR conditions, Δgfa1 exhibits compromised growth, reduced conidiation, defective germination, impaired cell wall integrity, and increased sensitivity to endoplasmic reticulum (ER) stress and high temperatures. Additionally, Δgfa1 demonstrates disruptions in protein homeostasis and iron metabolism. Transcriptomic analysis of the mutant under PR conditions reveals significant alterations in carbohydrate and amino acid metabolism, unfolded protein response (UPR) processes, and iron assimilation. Importantly, Gfa1 is essential for A. fumigatus virulence, as demonstrated in Caenorhabditis elegans and Galleria mellonella infection models. CONCLUSIONS: These findings underscore the critical role of Gfa1 in fungal pathogenicity and suggest its potential as a therapeutic target for combating A. fumigatus infections.

Aspergillus fumigatus↗
PubMed2025

Methylation patterns of the nasal epigenome of hospitalized SARS-CoV-2 positive patients reveal insights into molecular mechanisms of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has varied presentations from asymptomatic to death. Efforts to identify factors responsible for differential COVID-19 severity include but are not limited to genome wide association studies (GWAS) and transcriptomic analysis. More recently, variability in host epigenomic profiles have garnered attention, providing links to disease severity. However, whole epigenome analysis of the respiratory tract, the target tissue of SARS-CoV-2, remains ill-defined. RESULTS: We interrogated the nasal methylome to identify pathophysiologic drivers in COVID-19 severity through whole genome bisulfite sequencing (WGBS) of nasal samples from COVID-19 positive individuals with severe and mild presentation of disease. We noted differential DNA methylation in intergenic regions and low methylated regions (LMRs), demonstrating the importance of distal regulatory elements in gene regulation in COVID-19 illness. Additionally, we demonstrated differential methylation of pathways implicated in immune cell recruitment and function, and the inflammatory response. We found significant hypermethylation of the FUT4 promoter implicating impaired neutrophil adhesion in severe disease. We also identified hypermethylation of ELF5 binding sites suggesting downregulation of ELF5 targets in the nasal cavity as a factor in COVID-19 phenotypic variability. CONCLUSIONS: This study demonstrated DNA methylation as a marker of the immune response to SARS-CoV-2 infection, with enhancer-like elements playing significant roles. It is difficult to discern whether this differential methylation is a predisposing factor to severe COVID-19, or if methylation differences occur in response to disease severity. These differences in the nasal methylome may contribute to disease severity, or conversely, the nasal immune system may respond to severe infection through differential immune cell recruitment and immune function, and through differential regulation of the inflammatory response.

Humans↗
PubMed2025

Mitochondrial dysfunction fuels drug resistance in adult T-cell acute lymphoblastic leukemia.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a relatively rare hematological malignancy, characterized by the uncontrolled proliferation of immature T lymphoblasts and associated with a generally unfavorable prognosis. Our previous research has demonstrated that decreased mitochondrial activity is associated with the aggressiveness of T-ALL tumors. However, the mechanisms underlying this phenomenon and its contribution to treatment resistance remain largely elusive. METHODS: We have built up the largest known T-ALL tumor bank, with a median follow-up of 32 months, including our transcriptomic data from 79 newly sequenced tumors that adds to the 54 publicly accessible samples. Computational analyses and a series of functional assays were performed to investigate the molecular links between altered mitochondrial activity and drug resistance. RESULTS: The transcriptomic analysis revealed that down-regulation of mitochondrial activity is a potent driver of ABCB1 activation, a gene strongly associated with multidrug resistance. In tumors with low mitochondrial activity, the impaired fatty acids β-oxidation leads to intracellular lipid accumulation, which is directly involved in ABCB1 activation. Indeed, our data show that lipid neo-synthesis and accumulation promotes the activation of lipogenic transcription factors, liver X receptors (LXRs), which act as drivers of ABCB1 expression. Tumor data analyses confirmed that high ABCB1 expression in tumour samples is indeed associated with reduced mitochondrial gene expression, lipid droplet enrichment, increased tumour aggressiveness, and significantly shorter patient survival. CONCLUSIONS: Our study demonstrates that reduced mitochondrial activity drives multidrug resistance in adult T-ALL via lipid-mediated activation of ABCB1. These findings enhance our understanding of the biology of aggressive T-ALL and provide insight into mechanisms of resistance to conventional chemotherapy. Consequently, we propose that targeting de novo lipogenesis and restricting dietary fats, such as caprylic acid, may help overcome treatment resistance in patients with T-ALL exhibiting low mitochondrial activity. TRIAL REGISTRATION: The clinical trial was registered under the identifiers ChiCTR-ONRC-14004968 and ChiCTR2000031553 at ClinicalTrials.gov.

Adult↗
PubMed2026

Epigenetic alterations of AKT1 orchestrate a metabolic reprogramming in advanced lipedema: translational insights from an integrated multi-omics study.

BACKGROUND: lipedema is a chronic, progressive adipose disorder predominantly affecting women, characterized by painful, symmetrical subcutaneous fat accumulation, and typically resistant to lifestyle interventions. The pathophysiology of advanced-stage lipedema remains poorly defined, and no validated biomarkers or targeted therapies are currently available. METHODS: in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema. RESULTS: Genome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways. Transcriptomic analysis revealed profound downregulation of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation, alongside disruption of the sirtuin pathway and extracellular matrix remodeling. Integrative analysis pinpointed AKT1 as a central regulatory node: its promoter region was hypomethylated, correlating with increased gene expression and protein phosphorylation. Metabolomic profiling confirmed AKT1-linked metabolic dysregulation, including altered levels of L-arginine, NADP+, ATP, guanosine, glycerol, and glutamate, indicating impaired redox balance and energy metabolism. Trans-omic network analysis positioned AKT1 at the intersection of multiple dysregulated pathways, suggesting its key role in advanced-stage lipedema. CONCLUSIONS: the consistent enhancing of AKT pathway signaling across omic layers highlights its potential not only as a biomarker for disease stratification but also as a putative druggable target for therapeutic intervention. These findings offer new mechanistic insights into lipedema pathophysiology and provide a rationale for future personalized treatment strategies guided by AKT1-centric molecular profiling.

Proto-Oncogene Proteins c-akt↗
PubMed2026

BHLHE40 and ChREBP associate with hepatic enhancer clusters containing PPARα, RXRα, and HNF4 nuclear receptors.

BHLHE40/DEC1 is a basic helix-loop-helix transcription factor (TF) that regulates circadian rhythm and T-cell responses. In hepatocytes, its function and interplay with other TFs are poorly understood. Employing a genome-wide approach, we show that its genomic binding strongly overlapped with that of carbohydrate response-element binding protein, a sugar-sensing TF and known inducer of BHLHE40 expression. Transcriptomic analysis of primary mouse hepatocytes revealed reduced expression of genes involved in genomic stability on Bhlhe40 knockdown by siRNA. Bhlhe40 depletion potentiated fructose responsiveness of genes involved in cell-cycle regulation. Strikingly, genomic binding of BHLHE40 extensively overlapped with enhancers occupied by PPARα, RXRα, and HNF4 nuclear receptors and BHLHE40 fine-tuned the expression of PPARα target genes. Using HEK293 cells, we further observed that BHLHE40 physically interacted with RXRα and PPARα cofactors. Collectively, our data suggest that through cooperation with carbohydrate response-element binding protein and nuclear receptors, BHLHE40 is a central regulator of hepatic gene expression with potential to integrate inputs from nutrient signals contributing to the metabolic flexibility of the liver.

Animals↗
PubMed2006

The disparate nature of "intergenic" polyadenylation sites.

The termination of mature eukaryotic mRNAs occurs at specific polyadenylation sites located downstream from stop codons in the 3'-untranslated region (UTR). An accurate delineation of these sites is essential for the study of 3'-UTR-based gene regulation and for the design of pertinent probes for transcriptome analysis. Although typical poly(A) sites are located between 0 and 2 kb from the stop codon, EST sequence analyses have identified sites located at unexpectedly long ranges (5-10 kb) in a number of genes. Here we perform a complete mapping of EST and full-length cDNA sequences on the mouse and human genome to observe putative poly(A) sites extending beyond annotated 3'-ends and into the intergenic regions. We introduce several quality parameters for poly(A) site prediction and train a classification tree to associate P-values to predicted sites. We observe a higher than background level of high-scoring sites up to 12-15 kb past the stop codon, both in human and mouse. This leads to an estimate of about 5000 human genes having unreported 3'-end extensions and about 3500 novel polyadenylated transcripts lying in present "intergenic" regions. These high-scoring, long-range poly(A) sites corresponding to novel transcripts and gene extensions should be incorporated into current human and mouse gene repositories.

3' Untranslated Regions↗
PubMed2005

Detecting novel low-abundant transcripts in Drosophila.

Increasing evidence suggests that low-abundant transcripts may play fundamental roles in biological processes. In an attempt to estimate the prevalence of low-abundant transcripts in eukaryotic genomes, we performed a transcriptome analysis in Drosophila using the SAGE technique. We collected 244,313 SAGE tags from transcripts expressed in Drosophila embryonic, larval, pupae, adult, and testicular tissue. From these SAGE tags, we identified 40,823 unique SAGE tags. Our analysis showed that 55% of the 40,823 unique SAGE tags are novel without matches in currently known Drosophila transcripts, and most of the novel SAGE tags have low copy numbers. Further analysis indicated that these novel SAGE tags represent novel low-abundant transcripts expressed from loci outside of currently annotated exons including the intergenic and intronic regions, and antisense of the currently annotated exons in the Drosophila genome. Our study reveals the presence of a significant number of novel low-abundant transcripts in Drosophila, and highlights the need to isolate these novel low-abundant transcripts for further biological studies.

Animals↗
PubMed2004

A Genome-wide view of the Escherichia coli BasS-BasR two-component system implicated in iron-responses.

Histidine-to-aspartate (His-->Asp) phosphorelay (or two-component) systems are very common signal transduction mechanisms that are implicated in a wide variety of cellular responses to environmental stimuli in both prokaryotes and eukaryotes. Determination of the entire genomic sequence of Escherichia coli revealed that this gram-negative bacterium has 29 His-kinases and 32 response regulators. Of the 29 His-kinases, 23 have already been experimentally characterized at least to some extent in terms of their physiological functions. No physiological stimulus has yet been identified for each of the remaining 6 His-kinases (BasS, CreC, RstB, YfhK, YehU, and YpdA). Here we characterized the BasS-BasR two-component system with reference to its physiological function, taking genetic approaches together with genome-wide transcriptome profiling. First we showed that the hypothetical yfbE operon that appears to be implicated in the modification of lipopolysaccharides is regulated at the level of transcription in response to external iron, and then we showed that the BasS-BasR system is essential for this iron-dependent induction of yfbE. Another PhoQ-PhoP two-component system was also implicated in the full induction of yfbE in response to iron, but it was not essential. To gain more insight into the BasS-BasR system, we conducted genome-wide transcriptome analysis by microarray, finding that many of the uncovered putative iron-induced and BasS-BasR-dependent genes are somehow associated with acidic and/or anaerobic growth conditions. In this respect, it was found that mutant cells defective in the BasS-BasR system were sensitive to mild-acid growth conditions in the presence of a relatively high concentration of iron. These results are discussed with regard to a comprehensive picture of the His-->Asp phosphorelay signaling network in E. coli.

Aspartic Acid↗
PubMed2025

Tissue tropism, pathology, and pathogenesis of West Nile virus infection in saltwater crocodile (Crocodylus porosus).

West Nile virus (WNV) is one of the leading causes of economic losses to the saltwater crocodile farming industry due to skin lesions, known as "pix", induced by the infection. Our previous study suggested a possible immunopathological pathway causing these lesions. We therefore resolved to investigate the kinetics of WNV-infection and the elicited immune responses in experimentally challenged saltwater crocodile hatchlings. Employing virus isolation, quantitation of viral genome loads in tissues by RT-qPCR and immunohistochemistry, we demonstrated that upon infection, the virus replicates in the spleen, liver and later in the pancreas. Transcriptomic analysis, based on RNA sequencing and RT-qPCR of kidney and liver tissues, revealed that the early host response is primarily via alteration of cellular structure and metabolism. As the infection progresses, the response becomes predominantly inflammatory and antiviral. The results suggest that the kidney and gastrointestinal tract are primary nidi of viral replication leading to cloacal shedding, but a link to skin lesion development remains to be fully clarified.

Animals↗
PubMed2024

Editing of SlWRKY29 by CRISPR-activation promotes somatic embryogenesis in Solanum lycopersicum cv. Micro-Tom.

At present, the development of plants with improved traits like superior quality, high yield, or stress resistance, are highly desirable in agriculture. Accelerated crop improvement, however, must capitalize on revolutionary new plant breeding technologies, like genetically modified and gene-edited crops, to heighten food crop traits. Genome editing still faces ineffective methods for the transformation and regeneration of different plant species and must surpass the genotype dependency of the transformation process. Tomato is considered an alternative plant model system to rice and Arabidopsis, and a model organism for fleshy-fruited plants. Furthermore, tomato cultivars like Micro-Tom are excellent models for tomato research due to its short life cycle, small size, and capacity to grow at high density. Therefore, we developed an indirect somatic embryo protocol from cotyledonary tomato explants and used this to generate epigenetically edited tomato plants for the SlWRKY29 gene via CRISPR-activation (CRISPRa). We found that epigenetic reprogramming for SlWRKY29 establishes a transcriptionally permissive chromatin state, as determined by an enrichment of the H3K4me3 mark. A whole transcriptome analysis of CRISPRa-edited pro-embryogenic masses and mature somatic embryos allowed us to characterize the mechanism driving somatic embryo induction in the edited tomato cv. Micro-Tom. Furthermore, we show that enhanced embryo induction and maturation are influenced by the transcriptional effector employed during CRISPRa, as well as by the medium composition and in vitro environmental conditions such as osmotic components, plant growth regulators, and light intensity.

Solanum lycopersicum↗
PubMed2024

Inhibiting the expression of spindle appendix cooled coil protein 1 can suppress tumor cell growth and metastasis and is associated with cancer immune cells in esophageal squamous cell carcinoma.

Inhibiting the expression of spindle appendix cooled coil protein 1 (SPDL1) can slow down disease progression and is related to poor prognosis in patients with esophageal cancer. However, the specific roles and molecular mechanisms of SPDL1 in esophageal squamous cell carcinoma (ESCC) have not been explored yet. The current study aimed to investigate the expression levels of SPDL1 in ESCC via transcriptome analysis using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Moreover, the biological roles, molecular mechanisms, and protein networks involved in SPDL1 were identified using machine learning and bioinformatics. The cell counting kit-8 assay, EdU staining, and transwell assay were used to investigate the effects of inhibiting SPDL1 expression on ESCC cell proliferation, migration, and invasion. Finally, the correlation between the SPDL1 expression and cancer immune infiltrating cells was evaluated by analyzing data from the TCGA database. Results showed that SPDL1 was overexpressed in the ESCC tissues. The SPDL1 expression was related to age in patients with ESCC. The SPDL1 co-expressed genes included those involved in cell division, cell cycle, DNA repair and replication, cell aging, and other processes. The high-risk scores of SPDL1-related long non-coding RNAs were significantly correlated with overall survival and cancer progression in patients with ESCC (P < 0.05). Inhibiting the SPDL1 expression was effective in suppressing the proliferation, migration, and invasion of ESCC TE-1 cells (P < 0.05). The overexpression of SPDL1 was positively correlated with the levels of Th2 and T-helper cells, and was negatively correlated with the levels of plasmacytoid dendritic cells and mast cells. In conclusion, SPDL1 was overexpressed in ESCC and was associated with immune cells. Further, inhibiting the SPDL1 expression could effectively slow down cancer cell growth and migration. SPDL1 is a promising biomarker for treating patients with ESCC.

Humans↗
PubMed2025

Hatching of whipworm eggs induced by bacterial contact is serine-protease dependent.

Whipworms (Trichuris spp) are ubiquitous parasites of humans and domestic and wild mammals that cause chronic disease, considerably impacting human and animal health. Egg hatching is a critical phase in the whipworm life cycle that marks the initiation of infection, with newly hatched larvae rapidly migrating to and invading host intestinal epithelial cells. Hatching is triggered by the host microbiota; however, the physical and chemical interactions between bacteria and whipworm eggs, as well as the bacterial and larval responses that result in the disintegration of the polar plug and larval eclosion, are not completely understood. Here, we examined hatching in the murine whipworm, Trichuris muris, and investigated the role of specific bacterial and larval structures and molecules in this process. Using scanning and transmission electron microscopy, we characterised the physical interactions of both fimbriated (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) and non-fimbriated (Staphylococcus aureus) bacteria with the egg polar plugs during the induction/initiation stage, and visualised the effects of structural changes in the polar plugs, leading to larval eclosion. Further, we found that protease inhibitors blocked whipworm hatching induced by both fimbriated and non-fimbriated bacteria in a dose-dependent manner, suggesting the partial involvement of bacterial enzymes in this process. In addition, we identified the minimal egg developmental timing required for whipworm hatching, and transcriptomic analysis of T. muris eggs through embryonation revealed the specific upregulation of serine proteases (S01A family) in fully embryonated eggs containing 'hatch-ready' L1 larvae. Finally, we demonstrated that inhibition of serine proteases with the serine-protease inhibitor Pefabloc ablated T. muris egg hatching induced by bacteria. Collectively, our findings unravel the temporal and physicochemical bacterial-egg interactions leading to whipworm hatching and indicate serine proteases of both bacterial and larval origin mediate these processes.

Animals↗
PubMed2026

Effector loss and gain drives host range at a fitness cost.

Epidemic preparedness depends on tracking microbial evolution that drives shifts in ecological behaviors such as disease emergence. However, the genetic constraints mediating microbial emergence for generalist and specialist behaviors remain poorly described. Here, we addressed this question by combining comparative and functional genomics with phylogeny-based evolutionary analyses of the cereal pathogen Xanthomonas translucens. We show that a generalist X. translucens subgroup arose from a specialist ancestor, and the loss of a single effector gene, xopAL1, contributed to the generalist host expansion by promoting host jump from barley to wheat. Deleting barley-specialist X. translucens xopAL1 recapitulated the host jump to wheat and demonstrates risk across each globally distributed genetic lineage. However, this niche expansion via XopAL1 loss incurs a significant fitness cost to colonize barley. Moreover, the specialist lineage gained an additional effector gene, xopAJ, which enhanced virulence on barley while restricting oat infection, thereby reinforcing niche specialization. We further conducted transcriptomic analysis of wheat and determined that XopAL1 triggers a defense response that involves the reduction of photosynthetic processes. Our work provides an experimentally validated evolutionary framework to understand mechanisms of intergenera host jump. Overall, we demonstrate that single events of gene loss and gain shape ecological behaviors by creating a dynamic trade-off between niche breadth and specialization.

Triticum↗
PubMed2004

Genetics of dizygotic twinning: a feasibility study for a biobank.

To locate the genes that make a substantial contribution to variation in natural dizygotic twinning in humans, large-scale studies are needed. New studies should not stop at DNA genotyping, but collect material that allow gene-expression analysis, transcriptomics, proteomics and endocrinology. In this article we describe a pilot study to examine the feasibility, effectiveness and logistics of large-scale nationwide sample collection in Dutch families in which two or more sisters have given birth to spontaneous dizygotic twins. Pedigree data and addresses from family members of proband mothers were collected by telephone. Blood and urine samples were collected during a home visit, and handled in the afternoon. All participants were bled between 7 a.m. and 10 a.m. after overnight fasting. Blood samples of fertile women with a natural cycle were collected on the second, third or fourth day of their menstrual cycle. The effects of transportation and storage on blood quality, lipids, RNA with and without challenge, lymphocytes and other parameters were examined. Genomic DNA was isolated from blood and cells were immortalized using Epstein-Barr virus. In 78.6% of the women with a natural cycle blood samples were collected on the second, third or fourth day of the menstrual cycle. This percentage is likely to increase with the more dense geographical distribution of participants in the larger population. We conclude that the pilot study demonstrated the feasibility of this protocol to collect good quality of plasma, DNA, RNA and lymphocyte samples by home visits.

DNA↗
PubMed2026

Convergent IGF2 overexpression in pheochromocytoma/paraganglioma: insights from Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth and tumor predisposition, caused by dysregulated expression of genes on chromosome 11p15.5. An association between BWS and pheochromocytoma/paraganglioma (PPGL) has been suggested in isolated case reports over the past fifty years, but the molecular basis for this link remains unclear. We identified four patients with BWS who developed metastatic PPGL and investigated IGF2 pathway activation in these tumors and in PPGL across various genotypes. Pan-cancer transcriptomic analysis of The Cancer Genome Atlas (TCGA) demonstrated that PPGL overexpresses IGF2, with pseudohypoxic tumors exhibiting higher expression compared to other molecular clusters. Loss of heterozygosity and loss of imprinting at 11p15.5 partially explain this overexpression, with PPGL additionally demonstrating globally elevated expression of imprinted genes compared to most other tumor types, suggesting a broader relaxation of genomic imprinting. Cognate receptor profiling revealed that PPGLs are equipped to respond to IGF2 signaling, with high expression of IGF1R and insulin receptor isoform A (IR-A). Immunohistochemistry confirmed IGF2 protein overexpression in both BWS-associated and genotypically diverse sporadic PPGLs. Our results indicate that IGF2 overexpression is a convergent molecular feature of PPGL across genotypes and suggest the IGF2 pathway as a potential diagnostic and therapeutic target.

Humans↗
PubMed2004

Stress and survival of aging Escherichia coli rpoS colonies.

In Escherichia coli, the expression of the RpoS regulon is known to be crucial for survival in liquid cultures during stationary phase. By measuring cell viability and by transcriptome analysis, here we show that rpoS cells as well as wild-type cells survive when they form colonies on solid media.

Adaptation, Physiological↗
PubMed2006

Nonadditive regulation of FRI and FLC loci mediates flowering-time variation in Arabidopsis allopolyploids.

Allopolyploidy is formed by combining two or more divergent genomes and occurs throughout the evolutionary history of many plants and some animals. Transcriptome analysis indicates that many genes in various biological pathways, including flowering time, are expressed nonadditively (different from the midparent value). However, the mechanisms for nonadditive gene regulation in a biological pathway are unknown. Natural variation of flowering time is largely controlled by two epistatically acting loci, namely FRIGIDA (FRI) and FLOWERING LOCUS C (FLC). FRI upregulates FLC expression that represses flowering in Arabidopsis. Synthetic Arabidopsis allotetraploids contain two sets of FLC and FRI genes originating from Arabidopsis thaliana and A. arenosa, respectively, and flower late. Inhibition of early flowering is caused by upregulation of A. thaliana FLC (AtFLC) that is trans-activated by A. arenosa FRI (AaFRI). Two duplicate FLCs (AaFLC1 and AaFLC2) originating from A. arenosa are expressed in some allotetraploids but silenced in other lines. The expression variation in the allotetraploids is associated with deletions in the promoter regions and first introns of A. arenosa FLCs. The strong AtFLC and AaFLC loci are maintained in natural Arabidopsis allotetraploids, leading to extremely late flowering. Furthermore, FLC expression correlates positively with histone H3-Lys4 methylation and H3-Lys9 acetylation and negatively with H3-Lys9 methylation, epigenetic marks for gene activation and silencing. We provide evidence for interactive roles of regulatory sequence changes, chromatin modification, and trans-acting effects in natural selection of orthologous FLC loci, which determines the fate of duplicate genes and adaptation of allopolyploids during evolution.

Acetylation↗