SEARCH · PubMed Health

Results for “Key genes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources

PubMed1999

Differentiation: A central topic in developmental and cell biology.

The concept of "differentiation" encompasses all processes leading to differently specialized cell types, beginning with the progressive divergence of developmental pathways and ending with the successive programming and final elaboration of each particular cell type. Guidance and positional information are provided by external cues, by differentially allotted cytoplasmic determinants such as mRNA for transcription factors, and by cascades of intercellular signals. Eventually cell type specific selector genes, such as the muscle cell determining MyoD/myogenin genes and neural key genes (e. g., achaete scute-C, neurogenin), are switched on which control entire sets of subordinate effector genes. In multiplying cells "cell heredity" based on an epigenetic cellular memory enables transmission of the cell type determining program from parental to daughter cells. This memory can be based on autocatalytic self-activation of cell type specific selector genes and on the enduring action of gene groups such as the Polycomb and thrithorax complexes that code for proteins which bind to DNA sequences called cellular memory modules. These modules confer permanent accessibility (potentiation) or inaccessibility (silencing) upon many different gene loci on the chromosomes.

Animals↗

PubMed2005

Phylogenomic analysis of the PEBP gene family in cereals.

The TFL1 and FT genes, which are key genes in the control of flowering time in Arabidopsis thaliana, belong to a small multigene family characterized by a specific phosphatidylethanolamine-binding protein domain, termed the PEBP gene family. Several PEBP genes are found in dicots and monocots, and act on the control of flowering time. We investigated the evolution of the PEBP gene family in cereals. First, taking advantage of the complete rice genome sequence and EST databases, we found 19 PEBP genes in this species, 6 of which were not previously described. Ten genes correspond to five pairs of paralogs mapped on known duplicated regions of the rice genome. Phylogenetic analysis of Arabidopsis and rice genes indicates that the PEBP gene family consists of three main homology classes (the so-called TFL1-LIKE, MFT-LIKE, and FT-LIKE subfamilies), in which gene duplication and/or loss occurred independently in Arabidopsis and rice. Second, phylogenetic analyses of genomic and EST sequences from five cereal species indicate that the three subfamilies of PEBP genes have been conserved in cereals. The tree structure suggests that the ancestral grass genome had at least two MFT-like genes, two TFL1-like genes, and eight FT-like genes. A phylogenomic approach leads to some hypotheses about conservation of gene function within the subfamilies.

Base Sequence↗

PubMed2006

Gene expression in tumor-adjacent normal tissue is associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation.

Recurrence is a significant clinical problem for patients with rectal cancer treated with adjuvant chemoradiation. Previous studies have suggested that determining intratumoral gene expression of key genes may be helpful in predicting clinical outcome of patients with gastrointestinal malignancies undergoing chemotherapy. The role of molecular predictors for prediction of recurrence in the setting of adjuvant chemoradiotherapy is not well established. The present study was designed to identify a genetic profile that would be associated with recurrence in patients with rectal cancer treated with adjuvant chemoradiation therapy. A retrospective study with a longitudinal cohort and a cross-sectional cohort of 67 patients with locally advanced rectal cancer who underwent cancer resection, followed by 5-fluorouracil (5-FU) plus pelvic radiation was conducted. Total RNA was extracted from formalin-fixed, paraffin-embedded, laser-captured-microdissected tissue. We determined mRNA levels of genes involved in the 5-FU pathway (thymidylate synthase, dihydropyrimidine dehydrogenase), DNA-repair (excision-repair cross-complementing factor 1, Rad51), angiogenesis/radiation sensitivity [vascular endothelial growth factor (VEGF)] and radio-sensitivity [epidermal growth factor receptor (EGFR)] in tumor tissue and tumor-adjacent normal tissue by quantitative reverse transcriptase-polymerase chain reaction. In univariate analysis, only intratumoral gene expression level of VEGF (P = 0.055) was associated with recurrence, whereas elevated mRNA expression levels of thymidylate synthase (P = 0.008), VEGF (P = 0.023) and EGFR (P = 0.004) in tumor-adjacent normal tissue were significantly associated with recurrence. Multivariate analysis using recursive partitioning indicated that distinct groups of recurrence could be defined by elevated mRNA expression levels of VEGF, EGFR in tumor-adjacent normal tissue, and Rad51 in tumor tissue. These data suggest that the genetic profile of the tumor-adjacent normal tissue may be associated with treatment failure, indicating that tumor microenvironment may be more important in the development of recurrence of rectal tumors than formerly expected.

Adult↗

PubMed1994

Dorsal-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene.

Pattern formation in the dorsal region of the Drosophila embryo depends on the activity of a small group of zygotically acting genes. dpp, a key gene in this group, encodes a TGF-beta-like product (Dpp) that has been proposed to function as a morphogen with peak levels of Dpp-specifying amnioserosa, the dorsal-most cell type, and lower Dpp levels specifying dorsal ectoderm. The short gastrulation gene also contributes to patterning the dorsal region, but unlike the other genes involved in this process, sog activity is only required in ventral cells. Genetic evidence indicates that sog functions to antagonize dpp activity. In this report we present further phenotypic characterization of sog mutant embryos in dorsal and lateral regions and describe the cloning of the sog locus. sog is expressed in a broad lateral stripe of cells that abuts the dorsal territory of dpp-expressing cells. sog is predicted to encode a protein with an internal signal sequence and a large extracellular domain containing four repeats of a novel motif defined by the spacing of 10 cysteine residues that is distantly related to domains present in thrombospondin and procollagen. We propose that one or more of these cysteine repeats can be liberated by proteolytic cleavage of the primary Sog protein. These putative soluble Sog peptides may then diffuse into the dorsal region to antagonize the activity of Dpp, leading to the subdivision of the dorsal territory into amnioserosa and dorsal ectoderm.

Amino Acid Sequence↗

PubMed2005

Molecular characterization of sulfate-reducing bacteria in a New England salt marsh.

Sulfate reduction, mediated by sulfate-reducing bacteria (SRB), is the dominant remineralization pathway in sediments of New England salt marshes. High sulfate reduction rates are associated with the rhizosphere of Spartina alterniflora when plants elongate aboveground. The growth process concurrently produces significant amounts of new rhizome material belowground and the plants leak dissolved organic compounds. This study investigated the diversity of SRB in a salt marsh over an annual growth cycle of S. alterniflora by exploring the diversity of a functional gene, dissimilatory sulfite reductase (dsrAB). Because the dsrAB gene is a key gene in the anaerobic sulfate-respiration pathway, it allows the identification of microorganisms responsible for sulfate reduction. Conserved dsrAB primers in polymerase chain reaction (PCR) generated full-length dsrAB amplicons for cloning and DNA sequence analysis. Nearly 80% of 380 clone sequences were similar to genes from Desulfosarcina and Desulfobacterium species within Desulfobacteraceae. This reinforces the hypothesis that complete oxidizers with high substrate versatility dominate the marsh. However, the phylotypes formed several clades that were distinct from cultured representatives, indicating a greater diversity of SRB than previously appreciated. Several dsrAB sequences were related to homologues from gram-positive, thermophilic and non-thermophilic Desulfotomaculum species. One dsrAB lineage formed a sister group to cultured members of the delta-proteobacterial group Syntrophobacteraceae. A deeply branching dsrAB lineage was not affiliated with genes from any cultured SRB. The sequence data from this study will allow for the design of probes or primers that can quantitatively assess the diverse range of sulfate reducers present in the environment.

Cloning, Molecular↗

PubMed1995

Characterization of the polyketide synthase gene (pksL1) required for aflatoxin biosynthesis in Aspergillus parasiticus.

Aflatoxins are potent toxic and carcinogenic compounds, produced by Aspergillus parasiticus and A. flavus as secondary metabolites. In this research, a polyketide synthase gene (pksL1), the key gene for aflatoxin biosynthesis initiation in A. parasiticus, has been functionally identified and molecularly characterized. PCR-derived DNA probes were used to find the pksL1 gene from subtracted, aflatoxin-related clones. Gene knockout experiments generated four pksL1 disruptants which lost both the ability to produce aflatoxins B1, B2, and G1 and the ability to accumulate norsolorinic acid and all other intermediates of the aflatoxin biosynthetic pathway. A pksL1 DNA probe detected a 6.6-kb poly(A)+ RNA transcript in Northern (RNA) hybridizations. This transcript, associated with aflatoxin production, exhibited a regulated expression that was influenced by growth phase, medium composition, and culture temperature. DNA sequencing of pksL1 revealed an open reading frame for a polypeptide (PKSL1) of 2,109 amino acids. Sequence analysis further recognized four functional domains in PKSL1, acyl carrier protein, beta-ketoacyl-acyl carrier protein synthase, acyltransferase, and thioesterase, all of which are usually present in polyketide synthases and fatty acid synthases. On the basis of these results, we propose that pksL1 encodes the polyketide synthase which synthesizes the backbone polyketide and initiates aflatoxin biosynthesis. In addition, the transcript of pksL1 exhibited heterogeneity at the polyadenylation site similar to that of plant genes.

Aflatoxins↗

PubMed2003

Runx2/Cbfa1 functions: diverse regulation of gene transcription by chromatin remodeling and co-regulatory protein interactions.

Development of the osteoblast phenotype requires transcriptional mechanisms that regulate induction of a program of temporally expressed genes. Key components of gene activation, repression, and responsiveness to physiologic mediators require remodeling of the chromatin structure of a gene that renders promoter elements competent for the assembly of macromolecular transcriptional complexes. Here we review evidence that the Runx transcription factors support tissue-specific gene expression and bone formation by contributing to promoter structure, chromatin remodeling, and the integration of independent signaling pathways. In addition, we discuss the role of Runx2 in both activation and negative regulation of gene promoters (osteocalcin, bone sialoprotein, and Runx2/Cbfa1) in relation to the interaction of Runx with co-regulatory proteins in distinct subnuclear foci. The modifications in chromatin organization and transcription of the osteocalcin gene that are influenced by the activities of Runx2/Cbfa1 mediated by interacting proteins (YAP, TLE, SMAD, C/EBP) are emphasized. These functional properties of Runx2 provide novel insights into the requirements for multiple levels of transcriptional control within the context of nuclear architecture to support the convergence of regulatory signals that control tissue-specific gene expression.

Animals↗

PubMed2003

[Large-cell diffuse B-cell lymphoma: heterogenous origin and prognosis from the aspect of modern diagnosis].

BACKGROUND: Diffuse large B-cell lymphomas represent a heterogeneous group of tumors with a different origin, morphological findings and a variable clinical prognosis. These tumors have been recently classified into two prognostically relevant subgroups differing in the gene expression. The key genes suitable for routine diagnostics of DLBCL have not been yet identified. The aim of this work was to study changes and expression of several genes and proteins participating in the genesis of DLBCL. METHODS AND RESULTS: We analysed a group of 31 patients with diffuse large B-cell lymphomas. Basic clinical data including follow-up of the patients were available. Tumors were examined by a panel of immunohistochemical reactions with antibodies against CD20, CD79a, BCL-2, BCL-6, CD10, Ki-67 and TP53. FISH was used to detect a translocation t(14;18)(q32;q21) and/or a break in BCL6 region (3q27) suggestive of a translocation with a variable translocation partner t(3;?). PCR was utilized to detect the translocation t(14;18) and a clonal rearrangement of heavy and/or kappa chain of the immunoglobin genes. CONCLUSIONS: The expression of BCL-2 protein appeared to correlate with a higher mortality rate. The expression of other proteins examined in the study did not correspond significantly with the clinical development of the disease. Tumors with follicular lymphoma as a component had significantly higher mortality rate than the tumors developing de novo. Moreover, higher mortality was evident in cases with higher values of the International Prognostic Index (IPI).

DNA-Binding Proteins↗

PubMed2006

[Cloning the amidase gene from Rhodococcus rhodochrous M18 and its expression in Escherichia coli].

The amidase gene from Rhodococcus rhodochrous M18 was cloned by PCR amplification with primers developed by use of peptide amino acid sequences obtained after treating amidase with trypsin. Nucleotide sequence analysis of this gene revealed high homology with aliphatic amidases from R. erythropolis R312 and Pseudomonas aeruginosa. Considering the substrate specificity and the results of DNA analysis, amidase from R. rhodochrous M8 was assigned to the group of aliphatic amidases preferentially hydrolyzing short-chain aliphatic amides. The amidase gene was expressed in cells of Escherichia coli from the self promoter and from the lac promoter. To clone a fragment of R. rhodochrous M8 chromosome (approximately 9 kb), containing the entire structural gene and its flanking regions, plasmid pRY1 that can be integrated into the chromosome via homology regions was used. No sequences of the nitrile hydratase gene, the second key gene of nitrile degradation in strain R. rhodochrous M8, were detected. Thus, genes encoding amidase and nitrile hydratase in strain R. rhodochrous M8 are not organized into a single operon despite their common regulation.

Amidohydrolases↗

PubMed2002

SREBP-1: gene regulatory key to syndrome X?

Combined appearance of different cardiovascular risk factors seems to be more prevalent in individuals with decreased insulin sensitivity and increased visceral obesity, thereby being components of the so-called metabolic syndrome or syndrome X. Alterations in the abundance and activity of transcription factors lead to complex dysregulation of gene expression, which might be a key to understand insulin resistance-associated clinical clustering of coronary risk factors at the cellular or gene regulatory level. Recent examples are members of the nuclear hormone receptor superfamily-for example, peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding proteins (SREBPs). Besides their regulation by metabolites and nutrients, these transcription factors are also targets of hormones (like insulin and leptin), growth factors, inflammatory signals, and drugs. Major signaling pathways coupling transcription factors to extracellular stimuli are the MAP kinase cascades. We have recently shown that SREBPs appear to be substrates of MAP kinases and propose that SREBP-1 might play a role in the development of cellular features belonging to lipid toxicity and possibly syndrome X. Thus, the metabolic syndrome appears to be not only a disease or state of altered glucose tolerance, plasma lipid levels, blood pressure, and body fat distribution, but rather a complex clinical phenomenon of dysregulated gene expression.

Animals↗

PubMed2026

Genome-wide cis-expression Quantitative Trait Loci (eQTL) and transcriptomic signals reveal distinct molecular regulation across correlated feed efficiency traits.

INTRODUCTION: Feed efficiency (FE) is a complex trait which determines livestock production profitability, yet the molecular mechanisms behind it remain unclear. This study investigated the blood transcriptomic profile of lambs, alongside genotype data with the aim to uncover the genetic basis of FE traits such as absolute dry matter intake (DMIabsolute), DMI adjusted for body size (DMIadjusted), average daily live weight gain (ADG), and residual feed intake (RFI). MATERIALS AND METHODS: Bulk RNA-Seq and genotype data were analysed using three complementary approaches: differential gene expression (DGE) analysis, weighted gene co-expression network analysis (WGCNA), and cis-expression Quantitative Trait Loci (cis-eQTL) mapping. These methods were used independently to identify genes and regulatory networks associated with FE traits and to investigate evidence supporting multi-trait candidate gene selection. RESULTS: DGE analysis revealed 2, 24, 85 and 4 differentially expressed genes for DMIabsolute, DMIadjusted, ADG, and RFI (Padjusted < 0.05), functionally enriched in sensory perception, ATP-dependent chromatin remodeling, Notch signaling and immune response pathways. 9 gene modules significantly associated with the FE traits (P ≤ 0.05) with correlations ranging from r = -0.56 to 0.49, were identified using WGCNA. Single nucleotide polymorphism (SNP)-level cis-eQTL analysis identified 93 eSNPs associated with 74 genes (false discovery rate (FDR) < 0.05), while permutation-derived gene level analysis identified 280 eGenes (FDR < 0.2, empirical P < 0.03). Across the three analyses, applying thresholds of DGE (Padjusted < 0.05), WGCNA (correlation, P ≤ 0.05), and cis-eQTL gene-level significance (empirical P < 0.05), multiple overlapping genes were identified including DNMT3A, KANSL1, NCOR1 for DMIadjusted, ACOX2, FANCF, CIMIP2B, LOC101115106, ARMH2, LOC132657496 for ADG, and LOC114114576 for RFI representing regulators of variations in FE. DISCUSSION: The integration of DGE, WGCNA, and cis-eQTL analyses identified key genes and regulatory mechanisms associated with variation in FE traits. These results highlight that integrated multi-trait candidate gene identification approaches can reveal key genes that lower feed intake while maintaining animal growth, supporting breeding strategies aimed at improving efficiency and long-term economic sustainability in sheep.

average daily gain (ADG)↗

PubMed2001

Identification of a novel lipopolysaccharide-inducible gene with key features of both A kinase anchor proteins and chs1/beige proteins.

Mutations in chs1/beige result in a deficiency in intracellular transport of vesicles that leads to a generalized immunodeficiency in mice and humans. The function of NK cells, CTL, and granulocytes is impaired by these mutations, indicating that polarized trafficking of vesicles is controlled by CHS1/beige proteins. However, a molecular explanation for this defect has not been identified. Here we describe a novel gene with orthologues in mice, humans, and flies that contains key features of both chs1/beige and A kinase anchor genes. We designate this novel gene lba for LPS-responsive, beige-like anchor gene. Expression of lba is induced after LPS stimulation of B cells and macrophages. In addition, lba is expressed in many other tissues in the body and has three distinct mRNA isoforms that are differentially expressed in various tissues. Strikingly, LBA-green-fluorescent protein (GFP) fusion proteins are localized to vesicles after LPS stimulation. Confocal microscopy indicates this protein is colocalized with the trans-Golgi complex and some lysosomes. Further analysis by immunoelectron microscopy demonstrates that LBA-GFP fusion protein can localize to endoplasmic reticulum, plasma membrane, and endocytosis vesicles in addition to the trans-Golgi complex and lysosomes. We hypothesize that LBA/CHS1/BG proteins function in polarized vesicle trafficking by guiding intracellular vesicles to activated receptor complexes and thus facilitate polarized secretion and/or membrane deposition of immune effector molecules.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Detection of tissue-specific effects by methotrexate on differentiating mouse embryonic stem cells.

BACKGROUND: Pluripotent embryonic stem (ES) cells offer a unique possibility to monitor the differentiation of several cell types in vitro. This study attempts to identify marker genes during in vitro cell differentiation of murine ES cells and allow a prediction of chemical effects on cell differentiation of specific target tissues. The study focused on the expression pattern of key genes involved in cardiomyocyte and osteoblast differentiation: Oct-4, Brachyury, Nkx2.5, alpha myosin heavy chain, Cbfa1, and Osteocalcin. METHODS: Methotrexate was selected due to its well-characterized teratogenic effects. Several in vivo studies have demonstrated the specific interactions of methotrexate with bone formation whereas the cardiovascular system is not specifically affected after exposure to low concentration. The capability of murine ES cells to differentiate in vitro into cardiomyocytes as well as into osteoblasts have been used to demonstrate the target cell specificity in vitro, at non-cytotoxic concentration. RESULTS: Exposure of differentiating ES cells did not result in any gene profile modification of the selected cardiomyocyte specific genes, whereas the expression of osteoblast specific key genes, Cbfa1 and Osteocalcin, decreased. At the latter stages of skeletal differentiation we observed a 30% decrease in gene expression for Cbfa1 and a 60% decrease for Osteocalcin, with reference to the control. Early marker genes for undifferentiated cells and mesodermal cells were not modified after methotrexate treatment. CONCLUSIONS: These results show the possibility to integrate specific in vitro tests for teratogenicity in a test strategy for developmental toxicity.

Animals↗

PubMed2006

A bivalent chromatin structure marks key developmental genes in embryonic stem cells.

The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed "bivalent domains," consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.

Animals↗

PubMed2026

Metabolome-based genome-wide association study provides genetic insights into the andrographolide accumulation in Andrographis paniculata.

Andrographis paniculata is a distinctive medicinal plant that produces andrographolide-related metabolites, a class of diterpenoid compounds with potent anti-inflammatory activities. To elucidate the genetic mechanisms underlying the biosynthesis of these compounds, we perform comprehensive metabolic profiling and whole-genome resequencing on a natural population of A. paniculata. Population structure analysis reveals four distinct subgroups characterized by low intra-group genetic diversity but significant inter-group differentiation. Through metabolome-based genome-wide association study, we identify a significant locus associated with 14-deoxyandrographolide content. This locus harbors the candidate gene ApNB-ARC25 (CXN00004106), which encodes an NB-ARC domain-containing resistance protein. Functional characterization using virus-induced gene silencing shows that silencing of ApNB-ARC25 significantly reduces andrographolide accumulation and downregulates expressions of key genes in the andrographolide biosynthetic pathway. Heterologous overexpression of ApNB-ARC25 in rice not only improves resistance to blast disease but also enhances diterpenoid phytoalexin production. Our findings reveal that ApNB-ARC25 promotes diterpenoid accumulation and andrographolide biosynthesis by upregulating key genes involved in terpenoid backbone formation and diterpenoid synthesis. This work not only expands the functional understanding of the ApNB-ARC gene family but also provides a genetic resource for enhancing valuable compound accumulation in medicinal plants, offering important insights into the molecular regulation of medicinal metabolite biosynthesis.

Diterpenes↗

PubMed2024

Polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA) are associated with the PI3K-AKT pathway activation.

AIMS: We aimed to elucidate the mechanism leading to polycystic ovarian syndrome (PCOS) and recurrent spontaneous abortion (RSA). BACKGROUND: PCOS is an endocrine disorder. Patients with RSA also have a high incidence rate of PCOS, implying that PCOS and RSA may share the same pathological mechanism. OBJECTIVE: The single-cell RNA-seq datasets of PCOS (GSE168404 and GSE193123) and RSA GSE113790 and GSE178535) were downloaded from the Gene Expression Omnibus (GEO) database. METHODS: Datasets of PSCO and RSA patients were retrieved from the Gene Expression Omnibus (GEO) database. The "WGCNA" package was used to determine the module eigengenes associated with the PCOS and RSA phenotypes and the gene functions were analyzed using the "DAVID" database. The GSEA analysis was performed in "clusterProfiler" package, and key genes in the activated pathways were identified using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Real-time quantitative PCR (RT-qPCR) was conducted to determine the mRNA level. Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. RESULTS: The modules related to PCOS and RSA were sectioned by weighted gene co-expression network analysis (WGCNA) and positive correlation modules of PCOS and RSA were all enriched in angiogenesis and Wnt pathways. The GSEA further revealed that these biological processes of angiogenesis, Wnt and regulation of cell cycle were significantly positively correlated with the PCOS and RSA phenotypes. The intersection of the positive correlation modules of PCOS and RSA contained 80 key genes, which were mainly enriched in kinase-related signal pathways and were significant high-expressed in the disease samples. Subsequently, visualization of these genes including PDGFC, GHR, PRLR and ITGA3 showed that these genes were associated with the PI3K-AKT signal pathway. Moreover, the experimental results showed that PRLR had a higher expression in KGN cells, and that knocking PRLR down suppressed cell viability and promoted apoptosis of KGN cells. CONCLUSION: This study revealed the common pathological mechanisms between PCOS and RSA and explored the role of the PI3K-AKT signaling pathway in the two diseases, providing a new direction for the clinical treatment of PCOS and RSA.

Humans↗

PubMed2026

Crosstalk mediators implicated in the Stevens-Johnson Syndrome through gene regulatory network analysis.

Stevens-Johnson syndrome (SJS) is a rare and severe mucocutaneous disorder often triggered by medications or infections. Our previous research identified that four key genes, Ikzf1, Ptger3, Mavs, and Tlr3 are involved in SJS susceptibility and the conjunctival epithelial innate immune response, demonstrating their role in regulating interferon-stimulated genes. However, the interplay among these regulatory factors remains unclear. This study aimed to elucidate the crosstalk mechanisms between the pathways regulated by these four genes in conjunctival epithelial cells. We constructed a comprehensive gene regulatory network using transcriptomic data from murine conjunctival epithelial cells under 16 distinct conditions, including polyI:C stimulation across wild-type, knockout, and transgenic backgrounds for the key genes. A targeted network analysis systematically identified numerous candidate genes mediating the crosstalk between the regulatory pathways initiated by Ikzf1, Ptger3, Mavs, and Tlr3. The identified candidates suggest the involvement of diverse signaling pathways previously unlinked to SJS pathology. Our findings suggest that the pathogenesis of SJS may arise not from the dysfunction of isolated genes but from the disruption of a balance maintained by intricate pathway crosstalk.

Animals↗

PubMed2026

Adaptive Evolution of the PFK Gene Family in Chinese Longsnout Catfish, Leiocassis longirostris.

The Chinese longsnout catfish is a typical carnivorous fish with a relatively weak ability to utilize glucose. However, the genomic basis for its glucose metabolic adaptation remains unclear. In this study, we used comparative genomics methods to systematically analyze the evolutionary characteristics of glucose metabolism-related genes in the Chinese longsnout catfish, focusing on gene family evolution, patterns of expansion and contraction, and selective pressures. The results indicate that glucose metabolism-related genes have undergone significant reshaping during evolution. Genes involved in glucose digestion, absorption, and insulin signaling pathways demonstrate a tendency toward contraction, while those associated with protein and lipid metabolism exhibit expansion. This pattern is consistent with the species' long-term adaptation to a high-protein, high-fat diet. Comparative analysis further revealed that, compared to fish with different dietary habits, certain key genes involved in glycolysis in the Chinese longsnout catfish exhibit a reduction in copy number. Molecular evolutionary analysis showed that key genes involved in glycolysis and gluconeogenesis (including hexokinase 2 (hk2), phosphofructokinase, muscle/platelet (pfkm/p)) exhibit signs of accelerated evolution or positive selection. Notably, the PFK gene family exhibits complex evolutionary characteristics resulting from the combined effects of gene contraction, rapid evolution, and positive selection. In summary, this study reveals the genomic evolutionary basis for the glucose metabolic adaptation of the Chinese longsnout catfish and identifies the PFK gene family as a key candidate for elucidating its unique glucose metabolic characteristics.

Leiocassis longirostris↗