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PubMed2026

Molecular and immune profiling of HER2-low, HER2 ultra-low, and HER2-null male breast cancer.

BACKGROUND: HER2 expression is described along a biological continuum from null to positive and serves as a critical biomarker for therapeutic guidance in breast cancer (BC). While HER2-low and ultra-low categories have emerged as actionable targets for antibody-drug conjugates (ADCs) in female BC, their molecular and immune characteristics remain largely unexplored in male breast cancer. METHODS: We profiled 214 male breast tumors using next-generation sequencing and whole-transcriptome sequencing to assess mutational, transcriptomic, and immune landscapes. Tumor mutational burden (TMB) was defined as high if > 10 mutations/Mb. Immune cell fractions were inferred using Quantiseq deconvolution. RESULTS: Among 214 samples, 66 (30.8%) were HER2-null, 53 (24.8%) HER2 ultra-low, 80 (37.4%) HER2-low, and 15 (7.0%) HER2-positive. HER2 ultra-low tumors exhibited a higher prevalence of PIK3CA mutations (39.2% vs 22.6%, p ≤ 0.05) compared to HER2-null. No significant differences were observed in TMB-high frequency or PD-L1 expression across subgroups. Immune composition differed primarily between HER2-null and HER2-expressing subgroups: HER2-ultra-low tumors showed higher B-cell infiltration, whereas HER2-null tumors were enriched in neutrophils. Transcriptomic analysis revealed upregulation of selected stemness-associated genes (NANOG, KLF4, POU5F1) and CEACAM1 in HER2-null tumors, while HER2-low and HER2-ultra-low tumors were largely similar across most molecular and immune readouts in this cohort. CONCLUSIONS: HER2-null male breast cancer appears to represent the most biologically divergent subgroup within the HER2-negative spectrum, whereas HER2-low and HER2-ultra-low tumors were largely similar in this cohort. These findings support further investigation of HER2-null disease as a distinct biological state and provide hypothesis-generating data for biomarker development in this rare population.

Male↗

PubMed2026

Integrating transcriptomics and metabolomics reveals the molecular landscape of sperm maturation driven by regional differentiation in the epididymis of Guizhou-Guiqian semi-fine wool sheep.

Epididymal regionalized differentiation is crucial for sperm maturation. However, little is known about the synergistic remodeling mechanisms of different epididymal segments at the transcriptional and metabolic levels during sexual maturation in ruminants (especially sheep). We investigated the caput, corpus, and cauda epididymidis of pre-pubertal (2-month-old) and post-pubertal (7-month-old) Guizhou-Guiqian semi-fine wool sheep using histology, RNA sequencing, and metabolomics. Post-pubertal tissues exhibited increased luminal diameters, cilia lengths, and abundant cauda spermatozoa. Transcriptomic analysis revealed increasing differentially expressed genes (DEGs) along the caput-corpus-cauda axis (4642, 6103, and 7698 DEGs, respectively). Metabolomics detected 786 unique differentially accumulated metabolites (DAMs). Region-specific analysis showed that in the caput, up-regulated pathways (fructose/mannose metabolism; HK2, ALDOA, HKDC1) provide energy and substrates for initial sperm motility. In the corpus, down-regulated genes associated with extracellular matrix and tight junctions suggested epithelial barrier remodeling to establish an immune-tolerant microenvironment. The cauda specifically up-regulated the pentose phosphate pathway (FBP1, GPI) and glutathione metabolism, maintaining redox homeostasis for long-term sperm storage. Additionally, glycerophospholipid metabolism was enriched across all segments, where PEMT, AGPAT5, and LCAT likely regulate sperm plasma membrane fluidity. In conclusion, during sexual maturation, the caput drives energy metabolism and glycosylation, the corpus establishes immune tolerance, and the cauda maintains antioxidant homeostasis. The glycerophospholipid network throughout the across all epididymal segments synergistically remodels sperm membrane. This study reveals the underlying multi-omics regulatory mechanisms of epididymal functional differentiation, providing a theoretical basis for elucidating the molecular mechanisms of sperm maturation in this breed and for the molecular breeding of early reproductive performance in rams.

Animals↗

PubMed2025

A Functionally Conserved yet Dynamically Evolving Toolkit Underpinning Molluscan Biomineralization: Insights From Shell and Radula.

The molluscan shell and radula constitute pivotal molluscan innovations, each characterized by distinct functions and diverse forms, regulated by the highly specific biomineralization regulatory networks. Despite their paramount importance, the conserved components and adaptive evolutionary processes governing these regulatory networks remain unresolved. To address this knowledge gap, we advocate for the integration of data from less-explored lineages, such as Scaphopoda, as an essential step. This study presents the inaugural comprehensive transcriptome analysis of Pictodentalium vernedei, a representative species of Scaphopoda distinguished by a unique and evolutionarily conserved shell morphology and radula structure. Furthermore, comparative transcriptome/genome analyses are employed to unravel the conservatism and evolutionary innovation of the involved biomineralization regulatory elements. Our findings underscore the central role of secretomes in governing biomineralization processes, and we identified a fundamental set of 26 domains within molluscan secretomes, forming an essential functional protein domain repertoire necessary for the transformation of inorganic ions into biomineralized structures. This core biomineralization toolkit has undergone independent expansion and lineage-specific recruitment, giving rise to novel, modular domain architectures. This may be essential for the functional specialization and morphological diversification of shell and radula structures. These evolutionary processes are driven by the independent co-option of ancient genes and the emergence of novel de novo genes. This comprehensive investigation not only contributes insights into the evolution of molluscan biomineralization structures but also establishes avenues for further scholarly exploration.

Animals↗

PubMed2026

Environmental benzene exposure induces a conserved neutrophil degranulation program across species.

Immune systems have evolved under constant pressure from pathogens and environmental challenges, leading to the emergence of conserved defense mechanisms across diverse organisms. Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (≤5 ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.

Animals↗

PubMed2025

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗

PubMed2026

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44 °C) and compared with control conditions (27 ± 1 °C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals↗

PubMed2026

Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.

UNLABELLED: Breast and prostate cancers are both hormone-driven adenocarcinomas that undergo analogous invasion programs. Using lightsheet microscopy on intact tumors, we identified transitional junctions between precancerous and invasive regions. We then developed a multimodal serial-section workflow integrating volumetric reconstruction with spatial transcriptomics. Analysis of 319 spatial assays from 51 cases revealed gene expression features and novel structural insights defining the shift from precancer to invasive disease. In breast cancer, loss of MGP and PLAT was associated with invasive transition and promoted tumorigenesis in functional assays. In prostate cancer, GDF15, ALDH1A3, ANPEP, and FASN were upregulated along invasive progression, and their knockdown in PC-3 cells suppressed proliferation and migration. Enrichment of tumor-associated macrophages (SPP1+ and MS4A6A+) along non-triple-negative breast cancer breast cancer transitions highlights immune involvement as a potential driver of invasiveness. SIGNIFICANCE: Our method of defining precise spatial locations of invasive transition allows for the direct interrogation of transition drivers, presenting new therapeutic targets for the two most prevalent cancers and providing a framework for studying spatially defined mechanisms of tumor progression. See related commentary by Jing and Li, p. 1720.

Humans↗

PubMed2026

A Cooperative Release of Mitochondrial DNA From Platelets and Neutrophils Drives an Interferon Signature in Systemic Sclerosis.

OBJECTIVE: Mitochondria are organelles with a hypomethylated circular genome. Mitochondrial DNA (mtDNA) in the systemic circulation has been implicated in inflammation. This study investigates the role of circulating DNA in systemic sclerosis (SSc) and the cellular mechanisms governing its release. METHODS: Total DNA was isolated from the plasma of healthy controls (HCs) and patients with SSc. Copy numbers were analyzed for mtDNA (ATP-6) and GAPDH abundance by quantitative real-time polymerase chain reaction. mtDNA was isolated from HCs and patients with SSc. Neutrophils and platelets were incubated with the plasma and mtDNA of patients with SSc, and neutrophil extracellular trap (NET) formation was assessed by SytoxGreen and immunostainings. Platelets were tested for mtDNA release propensity. DNA oxidation was evaluated by MitoSOX Red staining in vitro and 8-OHdG enzyme-linked immunosorbent assay (ELISA) of patient plasma. Plasma interferon (IFN) type 1 and chemokine (C-X-C motif) ligand 4 (CXCL4) were measured by ELISA. IFN signaling activation capacity was evaluated using THP-1 reporter cells and confirmed by a whole blood bulk RNA transcriptomic analysis. RESULTS: Median plasma mtDNA levels were 152-fold higher in patients with SSc compared with HCs, whereas nuclear DNA levels were similar. mtDNA from SSc plasma was highly oxidized. SSc-derived mtDNA efficiently promoted its own release by NETosis, most potently in the neutrophils of patients with SSc and by platelet activation. Oxidized mtDNA from SSc platelets in complex with CXCL4 further stimulated mtDNA release in both neutrophils and platelets. mtDNA plasma concentrations correlated with type I IFN concentrations in the blood of patients with SSc, and SSc blood exhibited elevated IFN-stimulated gene expression. SSc plasma-derived mtDNA-induced IFN signaling and NET formation via endosomal Toll-like receptors, cyclic GMP-AMP synthase/stimulator of IFN genes, and the JAK/STAT pathway. The type I IFN pathway further promoted NETosis and mtDNA release because IFN receptor and JAK inhibition antagonized the proNETotic effects of IFN. CONCLUSION: SSc plasma is characterized by highly abundant mtDNA, which drives feedback loops amplifying its own release from both neutrophils and platelets. Thus, mtDNA contributes to inflammation and tissue damage in SSc.

Humans↗

PubMed2026

Dysregulation of U12-Type Splicing in Lupus Neutrophils.

OBJECTIVE: Neutrophil dysfunction is a hallmark of systemic lupus erythematosus (SLE), but its molecular basis remains unclear. This study explores transcriptional and posttranscriptional changes in low-density granulocytes (LDGs), a proinflammatory neutrophil subset expanded in SLE, focusing on NADPH oxidase (Nox) function and minor intron splicing. METHODS: LDGs and normal-density granulocytes (NDGs) were isolated from patients with SLE and healthy controls (HCs). CYBA (p22phox) expression was evaluated at transcript and protein levels. Nox activity was measured using luminol assays. Bulk RNA sequencing (RNA-seq) and rMATS software were used to assess alternative splicing, particularly of U12-type intron-containing genes. RESULTS: CYBA expression was reduced in SLE LDGs (n = 11) compared to SLE and HC NDGs (n = 6), with levels resembling those in chronic granulomatous disease neutrophils. SLE LDGs exhibited impaired Nox activity (n = 7 SLE, n = 12 HC). CYBA is a U12 intron-containing gene, and transcriptomic analysis revealed broad down-regulation of this gene class in SLE LDGs, suggesting minor spliceosome dysfunction. rMATS analysis showed increased U12-type intron retention and widespread splicing defects-including exon skipping and mutually exclusive exon use-in genes such as GBP5, MAEA, and STX10. These abnormalities were validated in an independent long-read RNA-seq data set from SLE peripheral blood mononuclear cells. Importantly, splicing disruptions correlated with disease activity and autoantibody profiles. CONCLUSION: Impaired U12-dependent splicing may contribute to neutrophil dysfunction in SLE, potentially via defective oxidative burst and altered immune regulation. These findings highlight the minor spliceosome as a novel player in lupus pathogenesis.

Humans↗

PubMed2007

Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets.

UNLABELLED: Hepatocellular carcinomas (HCCs) are a heterogeneous group of tumors that differ in risk factors and genetic alterations. We further investigated transcriptome-genotype-phenotype correlations in HCC. Global transcriptome analyses were performed on 57 HCCs and 3 hepatocellular adenomas and validated by quantitative RT-PCR using 63 additional HCCs. We determined loss of heterozygosity, gene mutations, promoter methylation of CDH1 and CDKN2A, and HBV DNA copy number for each tumor. Unsupervised transcriptome analysis identified 6 robust subgroups of HCC (G1-G6) associated with clinical and genetic characteristics. G1 tumors were associated with low copy number of HBV and overexpression of genes expressed in fetal liver and controlled by parental imprinting. G2 included HCCs infected with a high copy number of HBV and mutations in PIK3CA and TP53. In these first groups, we detected specific activation of the AKT pathway. G3 tumors were typified by mutation of TP53 and overexpression of genes controlling the cell cycle. G4 was a heterogeneous subgroup of tumors including TCF1-mutated hepatocellular adenomas and carcinomas. G5 and G6 were strongly related to beta-catenin mutations that lead to Wnt pathway activation; in particular, G6 tumors were characterized by satellite nodules, higher activation of the Wnt pathway, and E-cadherin underexpression. CONCLUSION: These results have furthered our understanding of the genetic diversity of human HCC and have provided specific identifiers for classifying tumors. In addition, our classification has potential therapeutic implications because 50% of the tumors were related to WNT or AKT pathway activation, which potentially could be targeted by specific inhibiting therapies.

Adenoma↗

PubMed2006

Transcriptome profiling in clinical breast cancer: from 3D culture models to prognostic signatures.

Early detection has been one of the most effective strategies to control the growing cancer burden. The power of earlier detection has been demonstrated by the impact of pap-smear, mammography, and PSA tests on cancer patient treatment and survival. These tests benefit patients independent of their genetic background or race. However, in many cases, we are still losing the battle against cancer because patients that initially presented with low-grade disease progress rapidly to aggressive forms of the disease. As of yet, we have limited means to predict a particular patient's fate or to specifically treat subtypes of cancer. A combination of earlier detection and targeted therapy, based on information from transcriptome analysis, could be a powerful ally in this battle. The theme of this review article is to briefly summarize innovative strategies using three-dimensional (3D) cell cultures of human mammary epithelial cells to predict clinical outcome in breast cancer. This strategy has the potential to further enhance our understanding of breast cancer biology and to contribute to the identification of biologically significant bio-markers that are also useful drug targets.

Biomarkers, Tumor↗

PubMed2026

A De Novo 16p13.3 Triplication Underlying Early-Onset Complex Neurodegeneration.

BACKGROUND: Neurodegenerative disorders are clinically and genetically heterogeneous, characterized by progressive neuronal loss and multidomain functional decline. Despite a presumed genetic etiology, a substantial proportion of cases remain molecularly undiagnosed. OBJECTIVE: The aim was to identify the genetic cause of an early-onset neurodegenerative disorder presenting with ataxia and cognitive impairment. METHODS: Rare copy-number variants were detected via short-read whole-genome sequencing (WGS), with candidate structural models inferred using long-read WGS. We performed transcriptomic profiling of peripheral blood leukocytes by RNA sequencing, with validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: We identified a de novo copy-number gain at 16p13.3. Combined copy-number profiling and long-read WGS suggested a candidate model comprising a triplicated segment in tandem with a proximal duplication, joined to a distal duplication via an inverted junction. Transcriptomic analysis demonstrated significant upregulation of ATP6V0C, AMDHD2, and PDPK1. CONCLUSIONS: These findings support a role for structural variation in early-onset neurodegeneration and highlight the value of combining short-read copy-number profiling with long-read WGS to detect and characterize complex genomic rearrangements. © 2026 International Parkinson and Movement Disorder Society.

16p13.3↗

PubMed2003

Protein arrays: the current state-of-the-art.

The completion of projects for sequencing whole genomes such as those of human, Saccaromyces cerevisiae and Caenorhabditis elegans has led to a rapid increase in the availability of genetic information. The technology by which such information is acquired is having a major impact on the way we think about analysing the RNA and protein products of the gene transcription. Transcriptome analysis has, via microarray technology, managed to achieve a near genomic scale quantitative analysis of mRNA levels. Several other technologies such as quantitative reverse transcriptase polymerase chain reaction and representational differential analysis are also available for analysing gene products. Traditionally, protein analysis has been performed by assaying one particular protein at a time, with very little parallel analysis. As protein function is a direct consequence of the protein product of the gene and as mRNA levels do not always correlate well with protein, it is desirable to analyse the entire protein complement of a cell etc. on a similar scale to mRNA. Despite the clear interest in analysing the expression, structure and function of proteins at a genomic scale, they have proven less amenable to such generic, high-throughput approaches. This review highlights the current thinking in the area of proteome analysis and considers the potential for future technology development in the area of protein arrays.

Animals↗

PubMed2006

Impact of the accessory gene regulatory system (Agr) on extracellular proteins, codY expression and amino acid metabolism in Staphylococcus epidermidis.

The quorum-sensing system Agr is part of a complex regulatory network of gene expression in staphylococci. This study presents the effect of an agr mutation on a biofilm-forming Staphylococcus epidermidis isolate by employing proteome and transcriptome analysis. The agr mutant exhibited a significantly lowered amount of extracellular proteins: amongst others SspA, AtlE, GehD and the phenol soluble modulins PSM1/2. Cytoplasmic proteome analysis and expression profiling indicated that the agr inactivation led to a strongly altered regulation of metabolism and virulence. Most strikingly, expression of CodY, a global regulator of virulence and stationary phase gene expression, was decreased in the agr mutant. In this respect, homologous genes known to be controlled by CodY in Bacillus subtilis and Lactococcus lactis were found to be up-regulated in the S. epidermidis agr mutant. The combined data show that wild-type and agr mutant differ with respect to amino acid biosynthesis and oligopeptide transport, carbohydrate utilization, as well as GMP and IMP interconversion. Due to the varying physiological properties S. epidermidis agr mutants, which often occur spontaneously, might be capable of colonizing alternative ecological niches in the human host and could, therefore, have an advantage in adapting to changing environmental conditions.

Amino Acids↗

PubMed2006

Gene expression changes in human cells after exposure to mobile phone microwaves.

Possible biological effects of mobile phone microwaves were investigated in vitro. In this study, which was part of the 5FP EU project REFLEX (Risk Evaluation of Potential Environmental Hazards From Low-Energy Electromagnetic Field Exposure Using Sensitive in vitro Methods), six human cell types, immortalized cell lines and primary cells, were exposed to 900 and 1800 MHz. RNA was isolated from exposed and sham-exposed cells and labeled for transcriptome analysis on whole-genome cDNA arrays. The results were evaluated statistically using bioinformatics techniques and examined for biological relevance with the help of different databases. NB69 neuroblastoma cells, T lymphocytes, and CHME5 microglial cells did not show significant changes in gene expression. In EA.hy926 endothelial cells, U937 lymphoblastoma cells, and HL-60 leukemia cells we found between 12 and 34 up- or down-regulated genes. Analysis of the affected gene families does not point towards a stress response. However, following microwave exposure, some but not all human cells might react with an increase in expression of genes encoding ribosomal proteins and therefore up-regulating the cellular metabolism.

Cell Line↗

PubMed2006

Expression profiling of proteins in L-threonine biosynthetic pathway of Escherichia coli by using antibody microarray.

We demonstrate the use of an antibody (Ab) microarray for a comparative expression profiling of proteins in an L-threonine biosynthetic pathway of Escherichia coli between a parental strain (W3110) and L-threonine overproducing mutant (TF5015). On the basis of a global comparative transcriptome analysis between the two strains, 28 analytical target proteins were selected and subjected to a production of polyclonal Abs against them. An Ab microarray was constructed by spotting a set of produced antibodies on a glass slide, and was employed for a comparative expression profiling of the proteins between the two strains by a two-color fluorescence assay method. The performance of the Ab microarray was evaluated with respect to cross-reactivity of the antibodies, dye-labeling efficiency, and the nature of antigenic proteins. Of these, the cross-reactivity of the used antibodies was found to mainly cause the deviation of the observed expression ratios from the expected ones. To offset the deviations, correction factors were derived from a statistical analysis and introduced. As a result, ten proteins were categorized to be up-regulated, while one was down-regulated in TF5015. Expression profiling of proteins using the Ab microarray was further verified by comparison with Western blotting and 2-DE.

Antibodies, Bacterial↗

PubMed2005

Bacterial toxins activating Rho GTPases.

The CNF1 toxin is produced by some uropathogenic (UPECs) andmeningitis-causing Escherichia coli strains. It belongs to a large family of bacterial virulence factors and toxins modifying cellular regulators of the actin cytoskeleton, namely the Rho GTPases. CNF1 autonomously enters the host cell cytosol, where it catalyzes the constitutive activation of Rho GTPases by deamidation. This activation is, however, attenuated because of activated Rho protein ubiquitin-mediated proteasomal degradation. Both Rho protein activation and deactivation confer phagocytic properties on epithelial and endothelial cells, as well as epithelial cell motility and cell-cell junction dynamics. Transcriptome analysis using DNA microarray revealed that endothelial cells respond to high doses of CNF1 by launching a genetic program of host alarm. This host cell reaction to CNF1 intoxication also indicates that degradation of activated Rho proteins by the proteasome may lead to a lowering of the threshold of the intoxicated cell inflammatory response. These results are consistent with growing evidence that Rho proteins control the cell inflammatory responses. It is tempting to assume that Rho deregulation may participate in various immunological disorders also involved in cancer.

Animals↗

PubMed2006

Methods and platforms for the quantification of splice variants' expression.

The relatively limited number of human protein encoding genes highlights the importance of the diversity generated at the level of the mRNA transcripts. As alternative RNA splicing plays a key role in mediating this diversity, it becomes critical to develop the tools and platforms that will deliver quantitative information on the specific expression levels associated with splice isoforms. This chapter describes the constraints generated by this global transcriptome analysis and the state-of-the-art techniques and products available to the scientific community.

Alternative Splicing↗