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24 pages, 1339 KB  
Article
Enhancing Thai Sentiment Analysis with WangchanBERTa and Instance-Class-Aware Dynamic Kernel Selection
by Panida Songram, Suchart Khummanee, Jirapond Muangprathub and Khanabhorn Kawattikul
Appl. Sci. 2026, 16(11), 5310; https://doi.org/10.3390/app16115310 - 25 May 2026
Viewed by 605
Abstract
Thai sentiment analysis on social media remains challenging due to the lack of explicit word boundaries, informal expressions, code-mixing, short text length, and severe class imbalance, particularly in the WISESIGHT benchmark dataset. Although transformer-based models such as WangchanBERTa provide strong contextual representations for [...] Read more.
Thai sentiment analysis on social media remains challenging due to the lack of explicit word boundaries, informal expressions, code-mixing, short text length, and severe class imbalance, particularly in the WISESIGHT benchmark dataset. Although transformer-based models such as WangchanBERTa provide strong contextual representations for Thai language processing, conventional hybrid architectures using fixed convolutional kernels may fail to capture diverse local semantic patterns across different sentiment classes. To address this limitation, this study proposes WangchanBERTa with Instance-Class-Aware Dynamic Kernel Selection (WangchanBERTa-IC-DKS), a novel hybrid framework that integrates contextualized embeddings with multi-kernel convolutional neural networks and dynamic kernel selection at both the instance and class levels. The proposed model adaptively determines kernel importance according to sentence semantics and class-specific sentiment characteristics, enabling more effective local feature extraction and improved minority-class recognition. Experiments were conducted on the WISESIGHT sentiment benchmark using four kernel candidates: [2, 3, 4], [3, 4, 5], [2, 3, 4, 5], and [1, 2, 3, 4, 5]. The kernel candidate [2, 3, 4, 5] achieves the best performance, with a mean macro-F1 of 63.93% averaged across three independent runs using different random seeds. Ablation studies further show that combining both class-aware and instance-aware dynamic kernel selection improves balanced classification performance compared with fixed multi-kernel CNN baselines. The proposed model also outperforms the previous state-of-the-art Parallel Hybrid model by 1.23 percentage points on the WISESIGHT dataset and by 1.36 percentage points on the 40 Thai children’s tales dataset. These findings demonstrate that dynamic kernel selection is more effective than fixed convolutional kernels across the two evaluated Thai sentiment benchmarks, particularly for short, noisy, and imbalanced Thai texts. Full article
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15 pages, 260 KB  
Article
Rewriting Desire: Intimacy, Identity, and Pleasure in Complex Storytelling 
by Francesca Medaglia
Humanities 2026, 15(2), 28; https://doi.org/10.3390/h15020028 - 9 Feb 2026
Viewed by 1222
Abstract
Desire, a transformative force, is one of contemporary serial narratives’ most intricate and multifaceted dimensions. Far from being reducible to a mere representation of sexual attraction, desire in television seriality operates as a prism through which to explore issues of intimacy, identity, and [...] Read more.
Desire, a transformative force, is one of contemporary serial narratives’ most intricate and multifaceted dimensions. Far from being reducible to a mere representation of sexual attraction, desire in television seriality operates as a prism through which to explore issues of intimacy, identity, and power. This paper seeks to analyze how desire is staged and problematised within a set of emblematic series that have significantly shaped contemporary cultural imagination. Grey’s Anatomy explores the entanglement of desire with professional life, emotional fragility, and collective trauma, constructing narratives where eros intersects with affective labour and the negotiation of identity within high-pressure contexts. Sex and the City proposes a very different model, placing female desire at the centre as a space of autonomy, experimentation, and confrontation with the normative frameworks of late capitalist society. By contrast, The Handmaid’s Tale reimagines desire within a dystopian theocracy, assigning it an overtly political function: here, erotic impulses and affective attachments become acts of resistance against systemic repression and biopolitical control. More recently, Sex Education embodies a cultural shift, presenting desire through a plural and inclusive lens that embraces diversity of sexual orientation, gender identity, and relational practices. These case studies, when viewed collectively, reveal how television series rework cultural codes of sexuality and intimacy, producing new imaginaries of the body, pleasure, and identity. In this perspective, serial narratives emerge as key cultural laboratories, reproducing and challenging dominant ideologies of desire while offering audiences opportunities for recognition, critique, and affective engagement beyond the screen. Full article
17 pages, 4071 KB  
Article
NKX6-3 in B-Cell Progenitor Differentiation and Leukemia
by Stefan Nagel, Corinna Meyer and Claudia Pommerenke
Genes 2025, 16(10), 1199; https://doi.org/10.3390/genes16101199 - 14 Oct 2025
Viewed by 1145
Abstract
Early B-cell development is primarily regulated at the transcriptional level and comprises the consecutive differentiation stages B-cell progenitor, pro-B-cell and pre-B-cell. These entities provide the cells of origin in B-cell precursor acute lymphoid leukemia (BCP-ALL) that show aberrations of developmental transcription factors (TFs), [...] Read more.
Early B-cell development is primarily regulated at the transcriptional level and comprises the consecutive differentiation stages B-cell progenitor, pro-B-cell and pre-B-cell. These entities provide the cells of origin in B-cell precursor acute lymphoid leukemia (BCP-ALL) that show aberrations of developmental transcription factors (TFs), representing major oncogenic drivers. Analysis of physiological TFs in these developmental entities helps us to understand their normal and disturbed activities and regulatory connections. Here, we focused on NKL-subclass homeodomain TF NKX6-3, which is active in both normal B-cell progenitors and TCF3::PBX1 fusion gene-positive BCP-ALL cases. By performing siRNA-mediated knockdown and forced expression experiments in BCP-ALL model cell lines, we established a gene regulatory network for NKX6-3 together with TALE-class homeodomain TFs IRX1 and MEIS1, as well as ETS-TF SPIB. Importantly, NKX6-3 was activated by TCF3::PBX1, underlying their co-expression in BCP-ALL. Furthermore, comparative expression profiling analysis of public BCP-ALL patient data revealed TGFb-pathway in-hibitor CD109 as a downregulated target gene of NKX6-3. TGFb-signalling, in turn, enhanced NKX6-3 expression, indicating mutual activation. Finally, RNA-seq analysis of BCP-ALL cell line RCH-ACV after NKX6-3 knockdown revealed MPP7 as an upregulated target gene of both NKX6-3 and TCF3::PBX1, revealing a role for the HIPPO-pathway in B-cell progenitors and TCF3::PBX1-positive BCP-ALL. Collectively, our data introduce novel players and regulatory connections to normal and aberrant TF-networks in B-cell progenitors to serve as potential diagnostic markers or therapeutic targets. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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14 pages, 657 KB  
Article
Buddhist Robes That Are and Are Not: Clothing, Desire, and Ambivalent Renunciation in The Tale of Genji
by Hyosook Kim
Religions 2025, 16(6), 735; https://doi.org/10.3390/rel16060735 - 7 Jun 2025
Cited by 1 | Viewed by 2998
Abstract
This study examines the symbolic ambiguity of Buddhist robes in the Heian period, focusing particularly on their representation in The Tale of Genji. While Buddhist monastic garments traditionally signify religious renunciation, they also functioned as fashion items regulated by strict social norms. [...] Read more.
This study examines the symbolic ambiguity of Buddhist robes in the Heian period, focusing particularly on their representation in The Tale of Genji. While Buddhist monastic garments traditionally signify religious renunciation, they also functioned as fashion items regulated by strict social norms. Through an analysis of Heian-era dress codes and deviations from them, as well as literary portrayals of robes associated with ordination scenes, this study reveals that robes embodied not only religious aspirations but also worldly attachments. Literary depictions highlight the tension between formal religious identity and persistent human desires, demonstrating how Buddhist robes served not only as religious symbols but also as mediators between spiritual ideals and secular emotions. By examining robes as visual and emotional media within a broader cultural and historical framework, this paper argues that Buddhist robes during the Heian period symbolized the complex intersection of salvation and desire. Ultimately, this study sheds light on how religious symbols, rather than representing pure spiritual transcendence, reveal the enduring contradictions inherent in human nature. Full article
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22 pages, 2618 KB  
Article
Is This the End of Anthropology as We Know It? Some Implication of FAIR Principles on Tales in Ethnological and Anthropological Qualitative Research
by Olga Orlić
Publications 2024, 12(4), 42; https://doi.org/10.3390/publications12040042 - 12 Nov 2024
Cited by 1 | Viewed by 4180
Abstract
Open science, accessibility and knowledge sharing, especially of articles and monographs stemming from publicly funded research, seem to be moving in quite a positive direction toward scientific development and have received almost unanimous approval from the scientific community. However, when it comes to [...] Read more.
Open science, accessibility and knowledge sharing, especially of articles and monographs stemming from publicly funded research, seem to be moving in quite a positive direction toward scientific development and have received almost unanimous approval from the scientific community. However, when it comes to data sharing, the existing practice reveals a different picture, and not exclusively a discipline-dependent one. FAIR principles are developed and promoted as guiding tools for creating contextualized standards. The fact that data obtained by a qualitative methodology deserve special attention and treatment regarding the accessibility principle is recognized. Although FAIR principles provide ways to anonymize the data and interlocutors, individuals coming from smaller communities or even communities of practice can sometimes be easily recognized by members of the same community if data are openly accessed. Sometimes the interlocutors might agree with these terms, but sometimes they do not. According to the disciplinary code of ethics, a researcher is obliged to thoroughly describe the ways of the raw data management and usage, and in the case of mandatory raw data sharing (e.g., for receiving funding), it can inevitably impact the narratives collected. The prerogative to make all data open inevitably leads to autocensorship among interlocutors, i.e., resulting in a kind of FAIRy tale being collected. The article discusses the results obtained from the survey carried out among Croatian ethnologists and cultural anthropologists about the currently practiced data sharing, their attitudes about data sharing and their perceived behavior in hypothetical situations connected with data sharing. The results show mixed opinions about data sharing and a desire to follow the disciplinary code of ethics first, i.e., to follow the interlocutors’ wishes in the case of data management and usage. Full article
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27 pages, 416 KB  
Article
Libertarian Populism? Making Sense of Javier Milei’s Political Discourse
by Reinhard Heinisch, Oscar Gracia, Andrés Laguna-Tapia and Claudia Muriel
Soc. Sci. 2024, 13(11), 599; https://doi.org/10.3390/socsci13110599 - 4 Nov 2024
Cited by 15 | Viewed by 31280
Abstract
This study seeks to understand the political discourse of Javier Milei and to determine which concept of populism best captures his approach. Although perceived by many as a populist, Milei is unusual in that he sees himself as a liberal libertarian and defender [...] Read more.
This study seeks to understand the political discourse of Javier Milei and to determine which concept of populism best captures his approach. Although perceived by many as a populist, Milei is unusual in that he sees himself as a liberal libertarian and defender of the West against collectivist policies. To this end, this study analyzes selected speeches by Milei from three different periods during and after the 2024 presidential election campaign and applies a deductive coding scheme designed to identify ideational populism, populist discursive framing, populism as strategy, and populism as crisis performance. The analysis confirms that Milei is at best a partial populist, as he fails to define the core populist concept of “the people”. It concludes that the concept of crisis performance emerges as the most apt theoretical framework to classify Milei’s type of populism. By rhetorically transforming the crisis not only into an existential economic issue but also into a moral tale of corruption and failure at the highest levels, he can appeal for radical change and offer himself as the national political savior. Milei’s discourse also illustrates that, unlike ideological populism or discursive populist framing, in the performative turn, the victims of the crisis, the people, often remain a vague signifier defined by their suffering at the hands of elites. Full article
15 pages, 4619 KB  
Article
Identification of Gene Regulatory Networks in B-Cell Progenitor Differentiation and Leukemia
by Stefan Nagel and Corinna Meyer
Genes 2024, 15(8), 978; https://doi.org/10.3390/genes15080978 - 24 Jul 2024
Cited by 3 | Viewed by 2192
Abstract
Pro-B- and pre-B-cells are consecutive entities in early B-cell development, representing cells of origin for B-cell precursor acute lymphoid leukemia (BCP-ALL). Normal B-cell differentiation is critically regulated by specific transcription factors (TFs). Accordingly, TF-encoding genes are frequently deregulated or mutated in BCP-ALL. Recently, [...] Read more.
Pro-B- and pre-B-cells are consecutive entities in early B-cell development, representing cells of origin for B-cell precursor acute lymphoid leukemia (BCP-ALL). Normal B-cell differentiation is critically regulated by specific transcription factors (TFs). Accordingly, TF-encoding genes are frequently deregulated or mutated in BCP-ALL. Recently, we described TF-codes which delineate physiological activities of selected groups of TF-encoding genes in hematopoiesis including B-cell development. Here, we exploited these codes to uncover regulatory connections between particular TFs in pro-B- and pre-B-cells via an analysis of developmental TFs encoded by NKL and TALE homeobox genes and by ETS and T-box genes. Comprehensive expression analyses in BCP-ALL cell lines helped identify validated models to study their mutual regulation in vitro. Knockdown and overexpression experiments and subsequent RNA quantification of TF-encoding genes in selected model cell lines revealed activating, inhibitory or absent connections between nine TFs operating in early B-cell development, including HLX, MSX1, IRX1, MEIS1, ETS2, ERG, SPIB, EOMES, and TBX21. In addition, genomic profiling revealed BCP-ALL subtype-specific copy number alterations of ERG at 21q22, while a deletion of the TGFbeta-receptor gene TGFBR2 at 3p24 resulted in an upregulation of EOMES. Finally, we combined the data to uncover gene regulatory networks which control normal differentiation of early B-cells, collectively endorsing more detailed evaluation of BCP-ALL subtypes. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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16 pages, 4279 KB  
Article
Chronic Lead Exposure in Adult Mice: Associations with miR-671/CDR1as Regulation, NF-κB Signaling, and Alzheimer’s Disease-like Pathology
by Mengyun Qiao, Haitao Yang, Li Liu, Tao Yu, Haihua Wang, Xiao Chen, Yi Zhang, Airu Duan, Shujun Lyu, Siyu Wu, Jingwei Xiao and Bin Li
Toxics 2024, 12(6), 410; https://doi.org/10.3390/toxics12060410 - 4 Jun 2024
Cited by 12 | Viewed by 3093
Abstract
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer’s disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology [...] Read more.
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer’s disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), β-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-β (Aβ), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis. Full article
(This article belongs to the Section Human Toxicology and Epidemiology)
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17 pages, 3690 KB  
Article
Establishment of the Myeloid TBX-Code Reveals Aberrant Expression of T-Box Gene TBX1 in Chronic Myeloid Leukemia
by Stefan Nagel, Josephine Haake, Claudia Pommerenke, Corinna Meyer and Roderick A. F. MacLeod
Int. J. Mol. Sci. 2024, 25(1), 32; https://doi.org/10.3390/ijms25010032 - 19 Dec 2023
Cited by 1 | Viewed by 3063
Abstract
T-box genes encode transcription factors, which control developmental processes and promote cancer if deregulated. Recently, we described the lymphoid TBX-code, which collates T-box gene activities in normal lymphopoiesis, enabling identification of members deregulated in lymphoid malignancies. Here, we have extended this analysis to [...] Read more.
T-box genes encode transcription factors, which control developmental processes and promote cancer if deregulated. Recently, we described the lymphoid TBX-code, which collates T-box gene activities in normal lymphopoiesis, enabling identification of members deregulated in lymphoid malignancies. Here, we have extended this analysis to cover myelopoiesis, compiling the myeloid TBX-code and, thus, highlighting which of these genes might be deregulated in myeloid tumor types. We analyzed public T-box gene expression datasets bioinformatically for normal and malignant cells. Candidate T-box-gene-expressing model cell lines were identified and examined by RQ-PCR, Western Blotting, genomic profiling, and siRNA-mediated knockdown combined with RNA-seq analysis and live-cell imaging. The established myeloid TBX-code comprised 10 T-box genes, including progenitor-cell-restricted TBX1. Accordingly, we detected aberrant expression of TBX1 in 10% of stem/progenitor-cell-derived chronic myeloid leukemia (CML) patients. The classic CML cell line K-562 expressed TBX1 at high levels and served as a model to identify TBX1 activators, including transcription factor GATA1 and genomic amplification of the TBX1 locus at 22q11; inhibitors, including BCR::ABL1 fusion and downregulated GNAI2, as well as BMP, FGF2, and WNT signaling; and the target genes CDKN1A, MIR17HG, NAV1, and TMEM38A. The establishment of the myeloid TBX-code permitted identification of aberrant TBX1 expression in subsets of CML patients and cell lines. TBX1 forms an integral part of an oncogenic regulatory network impacting proliferation, survival, and differentiation. Thus, the data spotlight novel diagnostic markers and potential therapeutic targets for this malignancy. Full article
(This article belongs to the Section Molecular Biology)
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12 pages, 2750 KB  
Review
The Role of IRX Homeobox Genes in Hematopoietic Progenitors and Leukemia
by Stefan Nagel
Genes 2023, 14(2), 297; https://doi.org/10.3390/genes14020297 - 23 Jan 2023
Cited by 9 | Viewed by 5064
Abstract
IRX genes are members of the TALE homeobox gene class and encode six related transcription factors (IRX1–IRX6) controlling development and cell differentiation of several tissues in humans. Classification of TALE homeobox gene expression patterns for the hematopoietic compartment, termed TALE-code, has revealed exclusive [...] Read more.
IRX genes are members of the TALE homeobox gene class and encode six related transcription factors (IRX1–IRX6) controlling development and cell differentiation of several tissues in humans. Classification of TALE homeobox gene expression patterns for the hematopoietic compartment, termed TALE-code, has revealed exclusive IRX1 activity in pro-B-cells and megakaryocyte erythroid progenitors (MEPs), highlighting its specific contribution to developmental processes at these early stages of hematopoietic lineage differentiation. Moreover, aberrant expression of IRX homeobox genes IRX1, IRX2, IRX3 and IRX5 has been detected in hematopoietic malignancies, including B-cell precursor acute lymphoblastic leukemia (BCP-ALL), T-cell ALL, and some subtypes of acute myeloid leukemia (AML). Expression analyses of patient samples and experimental studies using cell lines and mouse models have revealed oncogenic functions in cell differentiation arrest and upstream and downstream genes, thus, revealing normal and aberrant regulatory networks. These studies have shown how IRX genes play key roles in the development of both normal blood and immune cells, and hematopoietic malignancies. Understanding their biology serves to illuminate developmental gene regulation in the hematopoietic compartment, and may improve diagnostic classification of leukemias in the clinic and reveal new therapeutic targets and strategies. Full article
(This article belongs to the Special Issue Hox and TALE Gene Function in Evolution, Development, and Disease)
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18 pages, 4035 KB  
Article
Normal and Aberrant TALE-Class Homeobox Gene Activities in Pro-B-Cells and B-Cell Precursor Acute Lymphoblastic Leukemia
by Stefan Nagel and Corinna Meyer
Int. J. Mol. Sci. 2022, 23(19), 11874; https://doi.org/10.3390/ijms231911874 - 6 Oct 2022
Cited by 10 | Viewed by 3418
Abstract
Homeobox genes encode transcription factors regulating basic developmental processes. They are arranged according to sequence similarities of their conserved homeobox in 11 classes, including TALE. Recently, we have reported the so-called TALE-code. This gene signature describes physiological expression patterns of all active TALE-class [...] Read more.
Homeobox genes encode transcription factors regulating basic developmental processes. They are arranged according to sequence similarities of their conserved homeobox in 11 classes, including TALE. Recently, we have reported the so-called TALE-code. This gene signature describes physiological expression patterns of all active TALE-class homeobox genes in the course of hematopoiesis. The TALE-code allows the evaluation of deregulated TALE homeobox genes in leukemia/lymphoma. Here, we extended the TALE-code to include the stages of pro-B-cells and pre-B-cells in early B-cell development. Detailed analysis of the complete lineage of B-cell differentiation revealed expression of TALE homeobox genes IRX1 and MEIS1 exclusively in pro-B-cells. Furthermore, we identified aberrant expression of IRX2, IRX3 and MEIS1 in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) which originates from early B-cell progenitors. The data showed correlated activities of deregulated TALE-class members with particular BCP-ALL subtype markers, namely IRX2 with TCF3/E2A-fusions, IRX3 with ETV6/TEL-fusions, and MEIS1 with KMT2A/MLL-fusions. These correlations were also detected in BCP-ALL cell lines which served as experimental models. We performed siRNA-mediated knockdown experiments and reporter gene assays to analyze regulatory connections. The results showed mutual activation of IRX1 and TCF3. In contrast, IRX2 directly repressed wild-type TCF3 while the fusion gene TCF3::PBX1 lost the binding site for IRX2 and remained unaltered. IRX3 mutually activated fusion gene ETV6::RUNX1 while activating itself by aberrantly expressed transcription factor KLF15. Finally, KMT2A activated MEIS1 which in turn supported the expression of IRX3. In summary, we revealed normal TALE homeobox gene expression in early B-cell development and identified aberrant activities of IRX2, IRX3 and MEIS1 in particular subtypes of BCP-ALL. Thus, these TALE homeobox genes may serve as novel diagnostic markers and therapeutic targets. Full article
(This article belongs to the Section Molecular Oncology)
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19 pages, 6740 KB  
Article
The Hematopoietic TALE-Code Shows Normal Activity of IRX1 in Myeloid Progenitors and Reveals Ectopic Expression of IRX3 and IRX5 in Acute Myeloid Leukemia
by Stefan Nagel, Claudia Pommerenke, Corinna Meyer and Roderick A. F. MacLeod
Int. J. Mol. Sci. 2022, 23(6), 3192; https://doi.org/10.3390/ijms23063192 - 16 Mar 2022
Cited by 15 | Viewed by 4093
Abstract
Homeobox genes encode transcription factors that control basic developmental decisions. Knowledge of their hematopoietic activities casts light on normal and malignant immune cell development. Recently, we constructed the so-called lymphoid TALE-code that codifies expression patterns of all active TALE class homeobox genes in [...] Read more.
Homeobox genes encode transcription factors that control basic developmental decisions. Knowledge of their hematopoietic activities casts light on normal and malignant immune cell development. Recently, we constructed the so-called lymphoid TALE-code that codifies expression patterns of all active TALE class homeobox genes in early hematopoiesis and lymphopoiesis. Here, we present the corresponding myeloid TALE-code to extend this gene signature, covering the entire hematopoietic system. The collective data showed expression patterns for eleven TALE homeobox genes and highlighted the exclusive expression of IRX1 in megakaryocyte-erythroid progenitors (MEPs), implicating this TALE class member in a specific myeloid differentiation process. Analysis of public profiling data from acute myeloid leukemia (AML) patients revealed aberrant activity of IRX1 in addition to IRX3 and IRX5, indicating an oncogenic role for these TALE homeobox genes when deregulated. Screening of RNA-seq data from 100 leukemia/lymphoma cell lines showed overexpression of IRX1, IRX3, and IRX5 in megakaryoblastic and myelomonocytic AML cell lines, chosen as suitable models for studying the regulation and function of these homeo-oncogenes. Genomic copy number analysis of IRX-positive cell lines demonstrated chromosomal amplification of the neighboring IRX3 and IRX5 genes at position 16q12 in MEGAL, underlying their overexpression in this cell line model. Comparative gene expression analysis of these cell lines revealed candidate upstream factors and target genes, namely the co-expression of GATA1 and GATA2 together with IRX1, and of BMP2 and HOXA10 with IRX3/IRX5. Subsequent knockdown and stimulation experiments in AML cell lines confirmed their activating impact in the corresponding IRX gene expression. Furthermore, we demonstrated that IRX1 activated KLF1 and TAL1, while IRX3 inhibited GATA1, GATA2, and FST. Accordingly, we propose that these regulatory relationships may represent major physiological and oncogenic activities of IRX factors in normal and malignant myeloid differentiation, respectively. Finally, the established myeloid TALE-code is a useful tool for evaluating TALE homeobox gene activities in AML. Full article
(This article belongs to the Special Issue Transcriptional Regulation and Its Misregulation in Human Diseases)
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9 pages, 903 KB  
Review
The NKL- and TALE-Codes Represent Hematopoietic Gene Signatures to Evaluate Deregulated Homeobox Genes in Hodgkin Lymphoma
by Stefan Nagel
Hemato 2022, 3(1), 122-130; https://doi.org/10.3390/hemato3010011 - 2 Feb 2022
Cited by 3 | Viewed by 3513
Abstract
Homeobox genes encode transcription factors which control basic processes in development and differentiation. Concerning the sequence conservation in their homeobox, these genes are arranged into particular groups sharing evolutionary ancestry and resembling in function. We have recently described the physiological expression patterns of [...] Read more.
Homeobox genes encode transcription factors which control basic processes in development and differentiation. Concerning the sequence conservation in their homeobox, these genes are arranged into particular groups sharing evolutionary ancestry and resembling in function. We have recently described the physiological expression patterns of two homeobox gene groups, NKL and TALE, in early hematopoiesis and subsequent lymphopoiesis. The hematopoietic activities of eleven NKL and nine TALE homeobox genes have been termed as NKL- and TALE-codes, respectively. Due to the developmental impact of homeobox genes, these expression data indicate a key role for their activity in normal hematopoietic differentiation processes, including B-cell development. On the other hand, aberrant expression of NKL- and TALE-code members or ectopic activation of non-code members have been frequently reported in lymphoid malignancies, demonstrating their oncogenic potential in the hematopoietic compartment. Here, we provide an overview of the established NKL- and TALE-codes in normal lymphopoiesis and of deregulated homeobox genes in Hodgkin lymphoma, demonstrating the capability of gene codes to identify homeo-oncogenes in lymphoid malignancies. Full article
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18 pages, 3888 KB  
Article
NKL Homeobox Genes NKX2-3 and NKX2-4 Deregulate Megakaryocytic-Erythroid Cell Differentiation in AML
by Stefan Nagel, Claudia Pommerenke, Corinna Meyer and Roderick A. F. MacLeod
Int. J. Mol. Sci. 2021, 22(21), 11434; https://doi.org/10.3390/ijms222111434 - 22 Oct 2021
Cited by 13 | Viewed by 4012
Abstract
NKL homeobox genes encode transcription factors that impact normal development and hematopoietic malignancies if deregulated. Recently, we established an NKL-code that describes the physiological expression pattern of eleven NKL homeobox genes in the course of hematopoiesis, allowing evaluation of aberrantly activated NKL genes [...] Read more.
NKL homeobox genes encode transcription factors that impact normal development and hematopoietic malignancies if deregulated. Recently, we established an NKL-code that describes the physiological expression pattern of eleven NKL homeobox genes in the course of hematopoiesis, allowing evaluation of aberrantly activated NKL genes in leukemia/lymphoma. Here, we identify ectopic expression of NKL homeobox gene NKX2-4 in an erythroblastic acute myeloid leukemia (AML) cell line OCI-M2 and describe investigation of its activating factors and target genes. Comparative expression profiling data of AML cell lines revealed in OCI-M2 an aberrantly activated program for endothelial development including master factor ETV2 and the additional endothelial signature genes HEY1, IRF6, and SOX7. Corresponding siRNA-mediated knockdown experiments showed their role in activating NKX2-4 expression. Furthermore, the ETV2 locus at 19p13 was genomically amplified, possibly underlying its aberrant expression. Target gene analyses of NKX2-4 revealed activated ETV2, HEY1, and SIX5 and suppressed FLI1. Comparative expression profiling analysis of public datasets for AML patients and primary megakaryocyte–erythroid progenitor cells showed conspicuous similarities to NKX2-4 activating factors and the target genes we identified, supporting the clinical relevance of our findings and developmental disturbance by NKX2-4. Finally, identification and target gene analysis of aberrantly expressed NKX2-3 in AML patients and a megakaryoblastic AML cell line ELF-153 showed activation of FLI1, contrasting with OCI-M2. FLI1 encodes a master factor for myelopoiesis, driving megakaryocytic differentiation and suppressing erythroid differentiation, thus representing a basic developmental target of these homeo-oncogenes. Taken together, we have identified aberrantly activated NKL homeobox genes NKX2-3 and NKX2-4 in AML, deregulating genes involved in megakaryocytic and erythroid differentiation processes, and thereby contributing to the formation of specific AML subtypes. Full article
(This article belongs to the Special Issue Transcriptional Regulation and Its Misregulation in Human Diseases)
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22 pages, 5794 KB  
Article
Genome-Wide Identification and Characterization of TALE Superfamily Genes in Soybean (Glycine max L.)
by Liang Wang, Xinyu Yang, Yingqi Gao and Shouping Yang
Int. J. Mol. Sci. 2021, 22(8), 4117; https://doi.org/10.3390/ijms22084117 - 16 Apr 2021
Cited by 47 | Viewed by 4919
Abstract
The three-amino-acid-loop-extension (TALE) superfamily genes broadly existed in plants, which played important roles in plant growth, development and abiotic stress responses. In this study, we identified 68 Glycine max TALE (GmTALE) superfamily members. Phylogenetic analysis divided the GmTALE superfamily into the BEL1-like (BLH/BELL [...] Read more.
The three-amino-acid-loop-extension (TALE) superfamily genes broadly existed in plants, which played important roles in plant growth, development and abiotic stress responses. In this study, we identified 68 Glycine max TALE (GmTALE) superfamily members. Phylogenetic analysis divided the GmTALE superfamily into the BEL1-like (BLH/BELL homeodomain) and the KNOX (KNOTTED-like homeodomain) subfamilies. Moreover, the KNOX subfamily could be further categorized into three clades (KNOX Class I, KNOX Class II and KNOX Class III). The GmTALE genes showed similarities in the gene structures in the same subfamily or clade, whose coding proteins exhibited analogous motif and conserved domain compositions. Besides, synteny analyses and evolutionary constraint evaluations of the TALE members among soybean and different species provided more clues for GmTALE superfamily evolution. The cis-element analyses in gene promoter regions and relevant gene expression profiling revealed different regulating roles of GmTALE genes during soybean plant development, saline and dehydration stresses. Genome-wide characterization, evolution, and expression profile analyses of GmTALE genes can pave the way for future gene functional research and facilitate their roles for applications in genetic improvement on soybean in saline and dehydration stresses. Full article
(This article belongs to the Section Molecular Plant Sciences)
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