Expression Patterns Of Related Genes Research Articles

Role of Phenylpropanoid Pathway in Genetic Regulation and Physiological Adaptation in Arsenic Stressed Rice Genotypes

This study investigates the role of the phenylpropanoid pathway in arsenic (As) contaminated rice genotypes under natural conditions, exploring the intricate relationship between genetic regulation and physiological adaptation. Differential approaches adapted by rice genotypes to counteract As exposure are elucidated here through analysis of enzyme activities and related gene expression patterns, docking simulations, and nutrient dynamics. Enzymatic analysis from the phenylpropanoid pathway revealed significant variations across rice genotypes, with Mini mansoori exhibiting notably higher activity levels of key enzymes (PAL, C4H, 4CL, CHI, DFR and F3H) compared to Sampoorna and Pioneer. Additionally, the gene expression profiling unveiled differential responses, with Mini mansoori and Pioneer demonstrating higher expression of genes (OsPAL, OsCHS, OsCHI, OsF3H, OsF3'H, OsFLS, OsDFR, and OsLAR) associated with As resistance and tolerance, compared to Sampoorna. Enrichment analysis emphasized the involvement of cinnamic acid biosynthesis and related pathways. Molecular docking depicted certain proteins, such as Os4CL, OsFLS, OsDFR, and OsLAR susceptible to As binding, potentially affecting enzymatic activity. Ionomic analysis unveiled that Mini mansoori maintained higher levels of essential nutrients such as Na, Ca, P, Mn, Mg, and Zn in grains. However, this contrasted with Pioneer and Sampoorna, which experienced nutrient imbalance likely due to higher As accumulation. Chlorophyll fluorescence analysis depicted that Mini mansoori and Pioneer maintained better photosynthetic efficiency under As toxicity compared to Sampoorna. Moreover, network analysis highlights the critical role of Mg and Na interaction with essential phenolics and flavonoids, in combating the stress. Harnessing this understanding, targeted breeding effort could yield As-resistant rice varieties with enhanced nutrient and flavonoid contents, addressing both food safety and malnutrition in affected regions.

Genome sequencing analysis and validation of infestation-related functional genes of Vibrio parahaemolyticus LG2206 isolated from the hepatopancreas of diseased mud crab (Scylla paramamosain) in South China

Vibrio parahaemolyticus (V. parahaemolyticus) is a major bacterial pathogen found in brackish environments, leading to disease outbreaks and great economic losses in the mud crab industry. This study investigated the molecular mechanism of V. parahaemolyticus infecting mud crabs through genome sequencing analysis, survival experiments, and the expression patterns of related functional genes. A strain of V. parahaemolyticus with high pathogenicity and lethality was isolated from diseased mud crab in South China. The genome sequencing results showed that the genome size of V. parahaemolyticus was a circular chromosome of 3,357,271 bp, with a GC content of 45 %, containing 2985 protein-coding genes, denoted as V. parahaemolyticus LG2206. Genome analysis data revealed that a total of 113 adherence coding genes were obtained, including 120 virulence factor coding genes, 37 type III secretion system (T3SS) coding genes, and 277 sequences of T3SS effectors. Survival experiments showed that the mortality was 20 % within 96 h in the 1 × 104 CFU/mL infection group, 90 % in the 3.2 × 105 CFU/mL treatment group, and 100 % in the 1 × 106 CFU/mL treatment group. The LD50 of V. parahaemolyticus LG2206 was determined as 4.6 × 104 CFU/mL. Six genes of znuA and fliD (flagellin encoding genes), yscE and yscR (T3SS encoding genes), and nfuA and htpX (virulence factor encoding genes) were selected and validated by quantitative real-time PCR analysis after infection with 4.6 × 104 CFU/mL of V. parahaemolyticus LG2206 for 96 h. The expression of the six genes exhibited a significant up-regulation trend at all tested time points. The results indicated that the infestation-related genes screened in the experiment play important roles in the infestation process. This study provides timely and effective information to further analyze the molecular mechanism of V. parahaemolyticus infection and develop comprehensive measures for disease prevention and control.

Expression patterns of melanin-related genes are linked to crypsis and conspicuousness in a pumpkin toadlet.

Colour signals play pivotal roles in different communication systems, and the evolution of these characters has been associated with behavioural ecology, integumentary production processes and perceptual mechanisms of the species involved. Here, we present the first insight into the molecular and histological basis of skin colour polymorphism within a miniaturized species of pumpkin toadlet, potentially representing the lowest size threshold for colour polytypism in tetrapods. Brachycephalus actaeus exhibits a coloration ranging from cryptic green to conspicuous orange skin, and our findings suggest that colour morphs differ in their capability to be detected by potential predators. We also found that the distribution and abundance of chromatophores are variable in the different colour morphs. The expression pattern of coloration related genes was predominantly associated with melanin synthesis (including dct, edn1, mlana, oca2, pmel, slc24a5, tyrp1 and wnt9a). Up-regulation of melanin genes in grey, green and brown skin was associated with higher melanophore abundance than in orange skin, where xanthophores predominate. Our findings provide a significant foundation for comparing and understanding the diverse pathways that contribute to the evolution of pigment production in the skin of amphibians.

Gene choice in cancer cells is exclusive in ion transport but concurrent in DNA replication

Cancers share common cellular and physiological features. Little is known about whether distinctive gene expression patterns can be displayed at the single-cell level by gene families in cancer cells. The expression of gene homologs within a family can exhibit concurrence and exclusivity. Concurrence can promote all-or-none expression patterns of related genes and underlie alternative physiological states. Conversely, exclusive gene families express the same or similar number of homologs in each cell, allowing a broad repertoire of cell identities to be generated. We show that gene families involved in the cell-cycle and antigen presentation are expressed concurrently. Concurrence in the DNA replication complex MCM reflects the replicative status of cells, including cell lines and cancer-derived organoids. Exclusive expression requires precise regulatory mechanism, but cancer cells retain this form of control for ion homeostasis and extend it to gene families involved in cell migration. Thus, the cell adhesion-based identity of healthy cells is transformed to an identity based on migration in the population of cancer cells, reminiscent of epithelial-mesenchymal transition.

Characterization of Immunogenic Cell Death Related Molecular Subtypes and Its Therapeutic Implications for Prostate Adenocarcinoma

This study investigates immunogenic cell death (ICD)-related gene expression patterns in prostate adenocarcinoma (PRAD), explores the potential for ICD activation to induce anticancer effects, and identifies molecular subtypes in PRAD. Datasets from TCGA and GEO were analyzed using R software to assess ICD-related gene expression changes. Up-regulated genes included EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8, while down-regulated genes included IL1R, PIK3CA, IL17A, and others. Western blot confirmation supported the up-regulation of EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8. Clustering 497 samples based on 33 ICD-related genes revealed three molecular subtypes, with distinct gene functions and varying PD-L1 expression levels. The PRAD tumor microenvironment exhibited an abundance of resting dendritic cells and rare activated dendritic cells. This study suggests that diverse ICD-related genes are expressed in PRAD, leading to the classification of three molecular subtypes, which could guide precise molecular-level treatments. Additionally, the presence of resting dendritic cells in the PRAD tumor microenvironment hints at the potential for ICD-based therapies to activate these cells for anti-tumor effects.

Global dynamics and cytokinin participation of salt gland development trajectory in recretohalophyte Limonium bicolor.

Salt gland is an epidermal Na+ secretory structure that enhances salt resistance in the recretohalophyte sea lavender (Limonium bicolor). To elucidate the salt gland development trajectory and related molecular mechanisms, we performed single-cell RNA sequencing of L. bicolor protoplasts from young leaves at salt gland initiation and differentiation stages. Dimensionality reduction analyses defined 19 transcriptionally distinct cell clusters, which were assigned into four broad populations-promeristem, epidermis, mesophyll, and vascular tissue-verified by in situ hybridization. Cytokinin was further proposed to participate in salt gland development by the expression patterns of related genes and cytological evidence. By comparison analyses of scRNA-seq with exogenous application of 6-benzylaminopurine, we delineated five salt gland development-associated sub-clusters and defined salt gland specific differentiation trajectories from sub-clusters 8, 4, or 6 to sub-cluster 3 and 1. Additionally, we validated the participation of TRIPTYCHON and the interacting protein Lb7G34824 in salt gland development, which regulated the expression of cytokinin metabolism and signaling related genes such as GLABROUS INFLORESCENCE STEMS 2 to maintain cytokinin homeostasis during salt gland development. Our results generated a gene expression map of young leaves at single-cell resolution for the comprehensive investigation of salt gland determinants and cytokinin participation that helps elucidate cell fate determination during epidermis formation and evolution in recretohalophytes.

Identification and validation of neutrophils-related subtypes and prognosis model in triple negative breast cancer

BackgroundNeutrophils are considered to be crucial players in the initiation and progression of cancer. However, the complex relationship between neutrophils and cancer prognosis remains elusive, mainly due to the significant plasticity and diversity exhibited by these immune cells.MethodsAs part of our thorough investigation, we examined 38 Neutrophils-Related Genes (NRGs) and the associated copy number variations (CNV), somatic mutations, and gene expression patterns in relation to triple negative breast cancer (TNBC). The interactions between these genes, their biological roles, and their possible prognostic significance were then examined. With the NRGs as our basis, we applied Lasso and Cox regression analyses to create a predictive model for overall survival (OS). Furthermore, TNBC tissue and a public database were used to assess changes in MYO1D expression (MYO1D is characterized as a member of the myosin-I family, a group of motor proteins based on actin), its connection to neutrophil infiltration, and the clinical importance of MYO1D in TNBC.ResultsFour neutrophil-related genes were included in the development of a prognostic model based on neutrophils. The model was further shown to be an independent predicted factor for overall survival by multivariate Cox regression analysis. According to this study, neutrophil subtype B as well as gene subtype B, were associated with activated cancer immunity and poor prognosis of TNBC patients. Furthermore, considering that poor OS was linked to increased MYO1D expression, MYO1D was increased in TNBC tissues and associated with neutrophil infiltration. In vitro experiments also confirmed that MYO1D facilitates breast cancer invasion and metastasis.ConclusionBased on the degree of gene expression linked to neutrophils, a unique prognostic model was created. MYO1D could be a potential prognostic biomarker in TNBC patients and also a prospective target for therapy.

Restraint Stress-Induced Expression of Fos and Several Related Genes in the Hypothalamus of Hypertensive ISIAH Rats

Stress can play a significant role in arterial hypertension and many other complications of cardiovascular diseases. Considerable attention is paid to the study of the molecular mechanisms involved in the body response to stressful influences, but there are still many blank spots in understanding the details. ISIAH rats model the stress-sensitive form of arterial hypertension. ISIAH rats are characterized by genetically determined enhanced activities of the hypothalamic-pituitary-adrenocortical and sympathetic-adrenomedullary systems, suggesting a functional state of increased stress reactivity. For the first time, the temporal expression patterns of Fos and several related genes were studied in the hypothalamus of adult male hypertensive ISIAH rats after a single exposure to restraint stress for 30, 60, or 120 min. Fos transcription was activated and peaked 1 h after the start of restraint stress. The time course of Fos activation coincided with that of blood pressure increase after stress. Activation of hypothalamic neurons also alters the transcription levels of several transcription factor genes (Jun, Nr4a3, Jdp2, and Ppargc1a), which are associated with the development of cardiovascular diseases. Because Fos induction is a marker of brain neuron activation, activation of hypothalamic neurons and an increase in blood pressure were concluded to accompany increased stress reactivity of the hypothalamic-pituitary-adrenocortical and sympathoadrenal systems in hypertensive ISIAH rats during short-term restraint.

Constructing a folate metabolism gene signature for predicting prognosis in pulmonary neuroendocrine carcinomas.

Folate metabolism is a crucial biological process in cell proliferation and exhibits its pro-tumorigenic functions in multiple tumor types. However, its role in pulmonary neuroendocrine carcinomas remains uncertain. Folate metabolism related genes were obtained from previous studies, and the gene expression data and clinical data were collected from GEO database. The expression patterns of folate metabolism related genes were measured across normal and tumor tissues. We subsequently assessed their prognostic role using Kaplan-Meier and univariate Cox regression analysis. The core genes were isolated from 16 prognostic genes through four algorithms. Based on the expression of core genes, patients were divided into two clusters employing consensus clustering algorithm. Furthermore, we evaluated immune infltration level, biological mechanisms, and drug sensitivity. ALDH1L2 was finally identified through qRT-PCR and its pro-tumorigenic function was confirmed via in vitro experiments. The expression patterns of 26 folate metabolism related genes were evaluated between normal lung tissues and PNEC tumor tissues, and 20 of them exhibited differential expression. All of folate metabolism related genes were related to the prognosis of PNECS and 16 genes were identified as prognostic genes. Using SVM-RFE, RF, Xgboost and LASSO algorithm, three core genes were isolated from 16 prognostic genes. Based on the expression patterns of core genes, PNECs patients were divided into two clusters through consensus clustering algorithm. Cluster 1 was characterized by the worse survival, higher immune infiltration level, and sensitivity to chemotherapy. Compared with the HBEC cells, ALDH1L2 was notably overexpressed in NCI-H446 cells (SCLC cell line). ALDH1L2 knockdown significantly repressed the proliferation and migration capacity of tumor cells and increased the cell proportion in S phase. Our results indicated that folate metabolism gene signature is a reliable biomarker for PNECs. Classification based on this signature could be utilized to guide the treatment of PNECs patients and improve its prognosis.

Progesterone improved the behavior of PC12 cells under OGD/R by reducing FABP5 expression and inhibiting TLR4/NF-κB signaling pathway

Herein, PC12 cells were applied to detect the impact of progesterone under oxygen glucose deprivation/reperfusion (OGD/R) stimulation. The cell proliferation of PC12 cells was evaluated by cell counting kit-8 assay, and the concentrations of MDA, ROS and SOD were examined by their corresponding Enzyme Linked Immunosorbent Assay kits. The invasion and migration properties of PC12 cells were evaluated by transwell and wound healing assays, respectively. The expression patterns of related genes were evaluated by western blot and qPCR. Under OGD/R stimulation, progesterone treatment could elevate the viability of PC12 cells, reduce the levels of MDA and ROS, and elevate the concentration of SOD. Moreover, progesterone treatment could strengthen the invasion and migration abilities of PC12 cells under OGD/R condition, as well as decrease the apoptosis and inflammation. FABP5 expression was significantly increased in PC12 cells under OGD/R stimulation, which was reversed after progesterone stimulation. Under OGD/R stimulation, the protective effects of progesterone on PC12 cells were strengthened after si-FABP5 treatment. The protein levels of TLR4, p-P65 NF-κB, and P65 NF-κB in OGD/R-induced PC12 cells were increased, which were inhibited after progesterone treatment. Progesterone exerted protective effects on PC12 cells by targeting FABP5 under OGD/R stimulation.

Prognostic significance and expression pattern of glucose related genes in breast cancer: A comprehensive computational biology approach

Breast cancer (BC) is the most common type of malignancy globally and the main reason why women die from tumours. The Warburg effect, a characteristic of tumor, describes how most solid tumour cells acclimatize to their diverse surroundings by relying heavily on aerobic glycolysis for production of energy. In addition to producing key metabolic intermediates that are crucial for the production of macromolecules, which enable cancer cell division, invasiveness, and drug resistance, the transformed energy metabolism also supplies tumor cells with ATP for cellular energy. Here, we evaluated the expression profile, prognostic significance, and clinical relevance of glucose-related genes in BC using a bioinformatic approach. To clarify the significance of glucose-related genes in the development of breast tumours, we also performed a functional enrichment investigation of deregulated genes using the STRING and KEGG portal. The study depicted that of the 61 genes examined, 8 genes had a fold change </=± 1.5, that is, ADH1C, ADH4, ALDH1A3, ALDOC, FBP1, PCK1, PFKFB1, PFKFB3. Among the highly deregulated genes, ADH1C showed a fold change of −6.669. These deregulated genes were associated with poor prognosis. The study signifies that glucose related genes are highly dysregulated in breast cancer. Deregulation of glucose related genes is linked with a poor prognosis in BC individuals. Thus, targeting glucose related genes will provide an effective treatment approach for BC individuals.

Characterizing the SREB G protein-coupled receptor family in fish: Brain gene expression and genomic differences in upstream transcription factor binding sites

The SREB (Super-conserved Receptors Expressed in Brain) family of orphan G protein-coupled receptors is highly conserved in vertebrates and consists of three members: SREB1 (orphan designation GPR27), SREB2 (GPR85), and SREB3 (GPR173). SREBs are associated with processes ranging from neuronal plasticity to reproductive control. Relatively little is known about similarities across the entire family, or how mammalian gene expression patterns compare to non-mammalian vertebrates. In fish, this system may be particularly complex, as some species have gained a fourth member (SREB3B) while others have lost genes. To better understand the system, the present study aimed to: 1) use qPCR to characterize sreb and related gene expression patterns in the brains of three fish species with different systems, and 2) identify possible differences in transcriptional regulation among the receptors, using upstream transcription factor binding sites across 70 ray-finned fish genomes. Overall, regional patterns of sreb expression were abundant in forebrain-related areas. However, some species-specific patterns were detected, such as abundant expression of receptors in zebrafish (Danio rerio) hypothalamic-containing sections, and divergence between sreb3a and sreb3b in pufferfish (Dichotomyctere nigroviridis). In addition, a gene possibly related to the system (dkk3a) was spatially correlated with the receptors in all three species. Genomic regions upstream of sreb2 and sreb3b, but largely not sreb1 or sreb3a, contained many highly conserved transcription factor binding sites. These results provide novel information about expression differences and transcriptional regulation across fish that may inform future research to better understand these receptors.

Analysis of Genes Related to Invadopodia Formation and CTTN in Oral Squamous Cell Carcinoma-A Systematic Gene Expression Analysis.

Successful treatment for any type of carcinoma largely depends on understanding the patterns of invasion and migration. For oral squamous cell carcinoma (OSCC), these processes are not entirely understood as of now. Invadopodia and podosomes, called invadosomes, play an important role in cancer cell invasion and migration. Previous research has established that cortactin (CTTN) is a major inducer of invadosome formation. However, less is known about the expression patterns of CTTN and other genes related to it or invadopodia formation in OSCC during tumor progression in particular. In this study, gene expression patterns of CTTN and various genes (n = 36) associated with invadopodia formation were analyzed to reveal relevant expression patterns and give a comprehensive overview of them. The genes were analyzed from a whole genome dataset of 83 OSCC samples relating to tumor size, grading, lymph node status, and UICC (Union for Internatioanl Cancer Control). The data revealed significant overexpression of 18 genes, most notably CTTN, SRC (SRC proto-onocogene, non-receptor tyrosine kinase), EGFR (epidermal growth factor receptor), SYK (spleen associated tyrosine kinase), WASL (WASP like actin nucleation promotion factor), and ARPC2 (arrestin beta 1) due to their significant correlation with further tumor parameters. This study is one of the first to summarize the expression patterns of CTTN and related genes in a complex group of OSCC samples.

Effects of withering time of fresh leaves on the formation of flavor quality of Taiping Houkui tea

Withering time of fresh leaves is a key factor affecting the stability of flavor quality of Taiping Houkui tea (TPHK). It's effect and mechanism on the formation of flavor in TPHK remain unelucidated. Here, metabolomics and transcriptomics were combined to comprehensively investigate changes in the main flavor compounds and the expression patterns of related genes under different withering times. The results showed that withering had the greatest influence on the content of most amino acids and aroma volatiles. The relative content of most volatiles was observed to be highest at 6–8 h of withering time, which was consistent with the results from the sensory evaluation of aroma quality. Plant hormone signal transduction pathways played a key role in the variation of the flavor compound content under different withering times, especially ABA and JA signals. WGCNA demonstrated that ABA, JA, IAA, SA and different flavor substances were significantly associated with specific modules. JA may be involved in the metabolism of theanine during withering, while ABA may be involved in the accumulation of aromatic amino acids and main aroma components of TPHK. This research may serve as a reference for the optimization of the processing technology for TPHK.

Exorista sorbillans (Diptera: Tachinidae) parasitism shortens host larvae growth duration by regulating ecdysone and juvenile hormone titers in Bombyx mori (Lepidoptera: Bombycidae).

The tachinid fly, Exorista sorbillans, is a notorious ovolarviparous endoparasitoid of the silkworm, Bombyx mori, causing severe damage to silkworm cocoon industry. Silkworm larvae show typically precocious wandering behavior after being parasitized by E. sorbillans; however, the underlying molecular mechanism remains unexplored. Herein, we investigated the changes in the levels of 20-hydroxyecdysone (20E) and juvenile hormone (JH) titer, and they both increased in the hemolymph of parasitized silkworms. Furthermore, we verified the expression patterns of related genes, which showed an upregulation of 20E signaling and biosynthesis genes but a significant downregulation of ecdysone oxidase (EO), a 20E inactivation enzyme, in parasitized silkworms. In addition, related genes of the JH signaling were activated in parasitized silkworms, while related genes of the JH degradation pathway were suppressed, resulting in an increase in JH titer. Notably, the precocious wandering behavior of parasitized silkworms was partly recoverable by silencing the transcriptions of BmCYP302A1 or BmCYP307A1 genes. Our findings suggest that the developmental duration of silkworm post parasitism could be shortened by regulation of 20E and JH titers, which may help silkworm to resist the E. sorbillans infestation. These findings provide a basis for deeper insight into the interplay between silkworms and E. sorbillans and may serve as a reference for the development of a novel approach to control silkworm myiasis.

Characterization of TLR1 and expression profiling of TLR signaling pathway related genes in response to Aeromonas hydrophila challenge in hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × P. vachelli ♂).

Toll-like receptor 1 (TLR1) mediates the innate immune response to a variety of microbes through recognizing cell wall components (such as bacterial lipoproteins) in mammals. However, the detailed molecular mechanism of TLR1 involved in pathogen immunity in the representative hybrid yellow catfish (Pelteobagrus fulvidraco ♀ × P. vachelli ♂) has not been well studied. In the present study, we identified the TLR1 gene from the hybrid yellow catfish, and further comparative synteny data from multiple species confirmed that the TLR1 gene is highly conserved in teleosts. Phylogenetic analysis revealed distinguishable TLR1s in diverse taxa, suggesting consistence in evolution of the TLR1 proteins with various species. Structural prediction indicated that the three-dimensional structures of TLR1 proteins are relatively conserved among different taxa. Positive selection analysis showed that purifying selection dominated the evolutionary process of TLR1s and TLR1-TIR domain in both vertebrates and invertebrates. Expression pattern analysis based on the tissue distribution showed that TLR1 mainly transcribed in the gonad, gallbladder and kidney, and the mRNA levels of TLR1 in kidney were remarkably up-regulated after Aeromonas hydrophila stimulation, indicating that TLR1 participates in the inflammatory responses to exogenous pathogen infection in hybrid yellow catfish. Homologous sequence alignment and chromosomal location indicated that the TLR signaling pathway is very conserved in the hybrid yellow catfish. The expression patterns of TLR signaling pathway related genes (TLR1- TLR2 - MyD88 - FADD - Caspase 8) were consistent after pathogen stimulation, revealing that the TLR signaling pathway is triggered and activated after A. hydrophila infection. Our findings will lay a solid foundation for better understanding the immune roles of TLR1 in teleosts, as well as provide basic data for developing strategies to control disease outbreak in hybrid yellow catfish.

Abstract PD4-02: PD4-02 Spatial and temporal heterogeneity of predictive and prognostic signatures in triple-negative breast cancer treated with neoadjuvant combination immune-chemotherapy

Abstract Background: It is well known that immunological pathways are relevant for response to classical neoadjuvant chemotherapy as well as combined chemo-immunotherapy. In addition, it has been shown that combined chemo-immunotherapy significantly improves survival, even in the context of only moderate effects on pCR. Due to the window therapy with durvalumab-alone and the option to analyze multiple consecutive biopsies, the GeparNuevo trial offers the opportunity to 1) determine gene expression patterns for pCR and DDFS endpoints 2) identify pathways most relevant for pCR and DDFS 3) identify genes specifically regulated by immunotherapy (comparison of samples pre-and post-window) 4) identify genes specifically regulated by chemotherapy (comparison of samples pre-Tx and after 4 cycles of chemotherapy 5) identify longitudinal patterns of gene expression by comparison of up to four time points and 6) identify changes in the tumor microenvironment by spatial sequencing of tumor cell and stroma areas. Methods: 292 tumor samples were evaluated by gene expression analysis: 162 pretherapeutic core biopsies, 79 post-window biopsies, 32 biopsies during chemotherapy and 19 biopsies of the residual tumor after therapy. These samples were analyzed by HTG OBP panel targeting 2549 genes which are assigned to 25 different biological mechanisms or cellular pathways. In addition, spatial profiling was compared in a subset of pre-and post-window samples using Nanostring GeoMx spatial profiling system. Endpoints were pCR and DDFS. Results: A total of more than 600 genes were significantly associated with either the pCR or the DDFS endpoint in either the complete GeparNuevo cohort or one of the two therapy arms. Interestingly, there was a large number of predictive or prognostic genes (n=247 for pCR and n=179 for DDFS) in the durvalumab arm, while the number of genes in the placebo arm was considerably lower (n=113 for pCR and n=61 for DDFS). We used existing pathway information for HTG OBP panel to analyze the contribution of different cellular processes to pCR and DDFS signatures in different therapy arms. Immune pathways were particularly relevant for durvalumab signatures (pCR and DDFS), while cell cycle related gene expression patterns were particularly involved in signatures predictive of pCR in both therapy arms. To further assign genes to the cellular response to durvalumab-alone or chemotherapy-alone, we compared gene expression patterns in durvalumab arm before and after the window phase (gene expression patterns induced by one dose of durvalumab) with gene expression patterns in placebo arm before and after 4 cycles of chemotherapy. Further longitudinal alterations were analyzed by comparison of longitudinal samples for 4 different time-points (a: before NACT, n=162; b: after window phase, n=79; c: after 4 cycles, n=31 and d: at surgery, n=19). Using the Nanostring GeoMx spatial RNA profiling system guided by cytokeratine immunofluorescence, we compared areas with high tumor cell content with stromal areas with or without TILs. In combination with the HTG gene expression data, we were able allocate the changes induced by durvalumab vs chemotherapy to the stromal cell and tumor cell compartment, indicating a re-organization of the tumor-microenvironment. Conclusions: In our analysis, we show that immune gene signatures are particularly relevant for neoadjuvant response to durvalumab as well as prognosis after durvalumab treatment, while proliferation signatures are involved in pCR-signatures after durvalumab as well as chemotherapy. The spatial analysis showed that relevant changes occur in the stromal compartment, indicating a re-organization of the tumor microenvironment. The parallel targeting of immune- and proliferation pathways might explain why a combined immunotherapy-chemotherapy approach is more successful than each single therapy strategy alone. Citation Format: Carsten Denkert, Andreas Schneeweiss, Julia Rey, Akira Hattesohl, Thomas Karn, Michael Braun, Paul Jank, Jens Huober, Hans-Peter Sinn, Dirk-Michael Zahm, Claus Hanusch, Frederik Marmé, Jenny Furlanetto, Jörg Thomalla, Jens-Uwe Blohmer, Marion van Mackelenbergh, Thorsten Stiewe, Peter Staib, Christian Jackisch, Julia Teply-Szymanski, Peter A. Fasching, Bruno V. Sinn, Michael Untch, Karsten Weber, Sibylle Loibl. PD4-02 Spatial and temporal heterogeneity of predictive and prognostic signatures in triple-negative breast cancer treated with neoadjuvant combination immune-chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD4-02.

The transcriptional regulatory network of hormones and genes under salt stress in tomato plants (Solanum lycopersicum L.).

Salt stress has become one of the main limiting factors affecting the normal growth and development of tomatoes as well as fruit quality and yields. To further reveal the regulatory relationships between tomato hormones under salt stress, the interaction between hormones and TF and the genome-wide gene interaction network were analyzed and constructed. After salt treatment, the levels of ABA, SA, and JA were significantly increased, the levels of GA were decreased, and IAA and tZ showed a trend of first increasing and then decreasing. The expression patterns of hormone biosynthesis and signal transduction related genes were analyzed based on RNA-seq analysis, the co-expression network of hormones and genome-wide co-expression networks were constructed using weighted gene co-expression network analysis (WGCNA). The expression patterns of specific transcription factors under salt stress were also systematically analyzed and identified 20 hormone-related candidate genes associated with salt stress. In conclusion, we first revealed the relationship between hormones and genes in tomatoes under salt stress based on hormone and transcriptome expression profiles and constructed a gene regulatory network. A transcriptional regulation model of tomato consisted of six types of hormones was also proposed. Our study provided valuable insights into the molecular mechanisms regulating salt tolerance in tomatoes.

Effect of 1-methylcyclopropene on peel greasiness, yellowing, and related gene expression in postharvest 'Yuluxiang' pear.

'Yuluxiang' pear (Pyrus sinkiangensis) commonly develop a greasy coating and yellowing during storage. In this study, 1.0 μLL-1 1-methylcyclopropene (1-MCP) was applied to 'Yuluxiang' pear to investigate its effects on fruit quality, peel wax composition, greasiness index, chlorophyll content, and the expression pattern of related genes during storage at ambient temperature (25°C). The results showed that 1-MCP treatment maintained higher fruit firmness and chlorophyll content, decreased respiration rate, and postponed the peak of ethylene production rate, lowered the greasy index of the peel. The main wax components of peel accumulated during storage, the principal ones being alkenes (C23, C25, and C29), fatty acids (C16, C18:1, and C28), aldehydes (C24:1, C26:1, and C28:1), and esters (C22:1 fatty alcohol-C16 fatty acid, C22:1 fatty alcohol-C18:1 fatty acid, C22 fatty alcohol-C16 fatty acid, C22 fatty alcohol-C18:1 fatty acid, C24:1 fatty alcohol-C18:1 fatty acid, and C24 fatty alcohol-C18:1 fatty acid), and were reduced by 1-MCP. 1-MCP also decreased the expression of genes associated with ethylene biosynthesis and signal transduction (ACS1, ACO1, ERS1, ETR2, and ERF1), chlorophyll breakdown (NYC1, NOL, PAO, PPH, and SGR), and wax accumulation (LACS1, LACS6, KCS1, KCS2, KCS4, KCS10L, KCS11L, KCS20, FDH, CER10, KCR1, ABCG11L, ABCG12, ABCG21L, LTPG1, LTP4, CAC3, CAC3L, and DGAT1L). There were close relationships among wax components (alkanes, alkenes, fatty acids, esters, and aldehydes), chlorophyll content, greasiness index, and level of expression of genes associated with wax synthesis and chlorophyll breakdown. These results suggest that 1-MCP treatment decreased the wax content of 'Yuluxiang' pear and delayed the development of peel greasiness and yellowing by inhibiting the expression of genes related to the ethylene synthesis, signal transduction, wax synthesis, and chlorophyll degradation.

Transcriptomics Analysis Reveals a More Refined Regulation Mechanism of Methylation in a Drought-Tolerant Variety of Potato.

Whether DNA methylation modification affects the gene transcription and expression of potatoes under drought stress is still unknown. In this study, we used comparative transcriptomics to explore the expression pattern of related genes of the drought-tolerant variety Qingshu 9 (Q) and the drought-sensitive variety Atlantic (A) under drought stress and DNA methylation inhibitor treatment. The results showed that there was a significant difference in the number of DEGs between the two varieties' responses to mannitol and 5-azad C, especially when they were co-treated with two reagents, and the gene expression of Q was more sensitive to mannitol after two hours. Furthermore, we found that these differentially expressed genes (DEGs) were significantly enriched in DNA replication, transcription, translation, carbohydrate metabolism, photosynthesis, signal transduction, and glutathione metabolism. These results indicate that the difference in the background of methylation leads to the difference in drought resistance of the two varieties. The complexity of the DNA methylation of variety Q might be higher than that of variety A, and the method of methylation regulation is more refined. This study systematically expands the understanding of the molecular mechanism wherein DNA methylation regulates the response to drought stress.