Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences

RNA polymerase II, together with its catalytic subunit RPB1 (encoded by POLR2A), forms the core of the eukaryotic transcriptional machinery that drives the synthesis of protein-coding and regulatory RNA transcripts. Accumulating evidence indicates that dysregulation of POLR2A/RPB1 is a critical driver of oncogenesis, promoting uncontrolled proliferation, evasion of apoptosis, and extensive transcriptional reprogramming across multiple malignancies, frequently affected by recurrent 17p deletions co-occurring with major tumor suppressor loss events. Such coordinated genomic alterations create transcriptional dependency that may be exploited therapeutically. Beyond its canonical role in transcription, POLR2A/RPB1 operates within an extensive regulatory network involving non-coding RNAs. Notably, circular RNAs derived from the POLR2A transcript have emerged as stable post-transcriptional regulators that modulate tumorigenic signaling pathways. In these roles, circular POLR2A isoforms promote proliferation, migration, and therapy resistance in glioblastoma and clear-cell renal cell carcinoma by acting as miRNA sponges or by scaffolding protein complexes that activate pathways such as ERK. These findings suggest that disturbances in POLR2A function reshape not only transcriptional output but also the broader non-coding RNA landscape, thereby reinforcing malignant phenotypes. Moreover, pharmacological agents such as triptolide further highlight transcription-dependent vulnerabilities by destabilizing RPB1, offering promising therapeutic opportunities, particularly in drug-resistant cancers. Collectively, POLR2A/RPB1 emerges as a central node linking transcriptional control, noncoding RNA biogenesis, and oncogenic signaling, positioning it as a compelling candidate for biomarker development and targeted therapeutic intervention.

The corpus callosum (CC) is the largest interhemispheric commissure in the eutherian brain, enabling inter-hemispheric sensory integration and higher-order cognitive functions. Historically viewed through a neuron- and axon-centric lens, extensive research has established that glial cells (astrocytes, oligodendrocytes, and microglia) are essential regulators of CC ontogenesis. Astrocytic guidepost cells sculpt midline architecture and secrete axonal guidance cues; oligodendrocytes drive callosal axonal maturation and myelination; and microglia regulate their fasciculation and pruning, myelination patterns, and synaptic refinement. In addition to these cell-specific roles, coordinated bidirectional signaling between neurons and glia ensures that axon targeting, maturation, and interhemispheric integration proceed in a precisely orchestrated manner. Disruptions to these glial functions are implicated in congenital and developmental brain pathologies, including malformations and CC agenesis. This review integrates molecular, developmental, and translational insights to provide a comprehensive, mechanistic understanding of glial contributions to CC development and how their dysfunction shapes pathology.

Pectus excavatum (PE) a thoracic malformation may impact cardio-respiratory function, it could be perceived as esthetic problem particularly in young adults. The aim of study was to investigate the association between psychosocial determinants and exercise capacity in patients who underwent minimally invasive method of surgery - NUSS surgery. Fifty five patients (21.1 ± 3.0 years) were assessed 6.8 (±2.4) years after surgery. Controls were matched on sex, age and height to the intervention participants. Pulmonary function were comparable in both groups. Psychosocial functioning was assessed by the STAI questionnaires (anxiety as the trait and as the state) and the Beck Depression Inventory which were used to identify indicators of anxiety and depression, respectively, in participants who underwent surgery. Patients who underwent Nuss procedure had showed lower depression scores comparing to healthy controls, with BDI mean scores 5.7 thus within normal range. The anxiety as a state and as a trait scores were comparable in both groups, with results over normal range showing anxiety symptoms. For the whole group BDI scores negatively correlated with exercise capacity (6MWT distance and HR p<0.05). Anxiety scores were related to dyspnea with functional limitation ( p< 0.001) and nocturnal dyspnea p<0.05). Surgical intervention in patients with PE benefit in the context of psychological well-being and there are relations between depression and exercise capacity, anxiety and dyspnea perception in young adults in long term observation.

IntroductionThe aim of the study was to evaluate the effects of dietary supplementation with dried black chokeberry pomace (Aronia melanocarpa) on metabolic and antioxidant parameters in high-yielding dairy goats.Material and MethodsTwenty-seven Polish White Improved goats in mid-lactation were divided into three groups: a control group and two experimental groups receiving chokeberry pomace at 15 g/kg (A1) and 30 g/kg (A2) of dry matter in the feed. Biochemical, enzymatic, mineral, and oxidative stress parameters were analysed.ResultsSupplementation, particularly in group A2, improved the lipid profile by reducing low-density lipoprotein and triglycerides and increasing high-density lipoprotein levels. It also enhanced antioxidant capacity (higher glutathione and 2,2-diphenyl-1-picrylhydrazyl values) and positively influenced liver and lysosomal enzyme activity. Changes in creatinine, cholinesterase and creatine kinase levels were observed, along with correlations between calcium and metabolic markers.ConclusionThese findings suggest that chokeberry pomace may serve as a valuable feed additive in the nutrition of high-yielding dairy goats, promoting their metabolic health and potentially enhancing milk quality.

SummaryAcute myeloid leukaemia (AML) is a heterogeneous disease characterized by diverse genetic abnormalities. The standard of care remains to be chemotherapy and stem cell transplantation. In acute promyelocytic leukaemia (APL), differentiation therapy with all‐trans retinoic acid (ATRA) has significantly improved outcomes. Despite this, the success of ATRA has yet to be transferred to non‐APL AML. Exploring combinations to enhance the efficacy of ATRA in non‐APL AML remains a key focus. To investigate the therapeutic effect of ATRA in combination with cyclin‐dependent kinase 4/6 (CDK4/6) inhibitors in non‐APL AML. Non‐APL AML cell lines and primary patient samples were treated with ATRA and CDK4/6 inhibitors. Key outcomes included differentiation, proliferation, cell viability and colony‐forming capacity. Combination synergy was evaluated, and gene expression analysis identified pathways associated with therapeutic effects. The combination demonstrated dose‐dependent effects, enhancing differentiation and reducing proliferation, cell viability and colony‐forming capacity. A synergistic effect was observed across AML cell lines. Gene expression profiling revealed the co‐regulation of differentiation‐associated genes, unveiling the mechanisms driving therapeutic synergy. Combination of CDK4/6 inhibitors with ATRA shows potential for differentiation‐based AML treatment. This approach offers a promising avenue for improved outcomes in non‐APL AML.

The authors declare no competing interests. No data availability statement is needed as no data were generated, except the luciferase measurements but it is not usually required. Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract This study investigates the transformative role of Artificial Intelligence (AI) technologies in the agricultural sector, specifically focusing on their applications in enhancing animal welfare, health monitoring, and productivity. Over the last decade, advancements in AI, including machine learning, Internet of Things (IoT) systems, computer vision, and sensor technologies, have significantly enhanced livestock management across various species, including poultry, pigs, dairy cows, sheep and rodents. The study synthesizes findings from literature published between 2010 and 2022, highlighting how AI solutions facilitate comprehensive environmental monitoring, enable early disease detection, and support behavioral analysis, thereby optimizing production metrics and promoting better animal welfare practices. By employing the Technology Readiness Levels (TRL) framework, the review categorizes these technologies according to their developmental stages, from prototype to operational use, underscoring their increasing integration into commercial farming. Furthermore, the paper discusses the broader implications of AI adoption, including economic benefits, compliance with welfare standards, and sustainability objectives. The insights presented emphasize the need for continued research and innovation to fully harness AI’s potential in advancing animal management strategies and addressing the growing global demand for animal products. Overall, the findings confirm that AI technologies have demonstrated effectiveness in improving animal welfare, health monitoring, and productivity across diverse species and farming contexts.

Maintaining proteostasis is critical for neuronal health, with its disruption underpinning the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Nuclear Factor Erythroid 2-Related Factor 1 (NFE2L1) has emerged as a key regulator of proteostasis, integrating proteasome function, autophagy, and ferroptosis to counteract oxidative stress and protein misfolding. This review synthesizes current knowledge on the role of NFE2L1 in maintaining neuronal homeostasis, focusing on its mechanisms for mitigating proteotoxic stress and supporting cellular health, offering protection against neurodegeneration. Furthermore, we discuss the pathological implications of NFE2L1 dysfunction and explore its potential as a therapeutic target. By highlighting gaps in the current understanding and presenting future research directions, this review aims to elucidate NFE2L1's role in advancing treatment strategies for neurodegenerative diseases.