Response Regulation Research Articles

Oryza sativa Stress Associated Protein (OsSAP) Promoter Modulates Gene Expression in Response To Abiotic Stress by Utilizing Cis Regulatory Elements Within The Promoter Region

The occurrence of extreme weather patterns induced by climate change has resulted in abiotic stress problems impacting the growth and productivity of plants. Rice (Oryza sativa), a staple food source for most Asians, is similarly affected by these challenges. Previous studies have identified the Oryza sativa Stress Associated Protein (OsSAP) genes to play a significant role in responding to abiotic stress. Among the 18 Stress Associated Protein members, OsSAP4 was highly expressed during drought and salinity conditions. Therefore, further experiments have been conducted, focusing specifically on the promoter region, to comprehend its regulation in response to abiotic stresses. Various types of cis-elements binding sites have been identified within the OsSAP4 promoter, encompassing MYB, CAMTA, CPP, C3H, HDZIP, bZIP, WRKY, and ERF. However, promoter analysis revealed that the distribution of the Cis-Regulatory elements bound by the Ethylene Response Factor (ERF) was the most prominent in the OsSAP4 promoter. Consequently, an analysis of promoter regulation was conducted using GUS reporter in Arabidopsis thaliana (A. thaliana) on two different sizes of OsSAP4 promoter sequences, each containing different quantities of ERF transcription factor binding sites. A noticeable difference in GUS staining activity was observed between pOsSAP4(1524 pb)::GUS and pOsSAP4(460 pb)::GUS, where pOsSAP4(1524 pb)::GUS exhibited higher GUS staining activity than pOsSAP4(460 pb)::GUS. The differences in GUS staining analysis are evident at the vegetative stage (leaf), silique, and inflorescence stages. This implies the participation of various other cis-element binding sites that influence the expression pattern of the OsSAP4 promoter during abiotic stress.

Genome-wide analysis of the SWEET gene family and its response to powdery mildew and leaf spot infection in the common oat (Avena sativa L.)

The nutritional quality and yield of oats (Avena sativa) are often compromised by plant diseases such as red leaf, powdery mildew, and leaf spot. Sugars Will Eventually be Exported Transporters (SWEETs) are newly identified sugar transporters involved in regulating plant growth and stress responses. However, the roles of SWEET genes in biotic stress responses remain uncharacterized in oats. In this study, 13 AsSWEET genes were identified across nine chromosomes of the oat genome, all of which were predicted to contain seven transmembrane regions. Phylogenetic analysis revealed four clades of AsSWEET proteins, with high homology to SWEET proteins in the Poaceae family. Collinearity analysis demonstrated strong relationships between oat and Zea mays SWEETs. Using subcellular localization prediction tools, AsSWEET proteins were predicted to localize to the plasma membrane. Promoter analysis revealed cis-acting elements associated with light response, growth, and stress regulation. Six AsSWEET proteins were predicted to interact in a network centered on AsSWEET1a and AsSWEET11. Gene expression analysis of two oat varieties, ‘ForagePlus’ and ‘Molasses’, indicated significant expression differences in several AsSWEET genes following infection with powdery mildew or leaf spot, including AsSWEET1a, AsSWEET1b, AsSWEET2b, AsSWEET3a, AsSWEET11, and AsSWEET16. These SWEET genes are potential candidates for disease resistance in oats. This study provides a foundation for understanding the regulatory mechanisms of AsSWEET genes, particularly in response to powdery mildew and leaf spot, and offers insights for enhancing oat molecular breeding.

Current insights into apolipoprotein E and the immune response in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurological disorder and the most common cause of dementia. Genetic analyses identified apolipoprotein E (APOE) as the strongest genetic risk for late-onset AD. Studies have shown that ApoE modulates AD pathogenesis in part by influencing amyloid-β (Aβ) deposition. However, ApoE also appears to regulate elements of AD via regulation of innate immune response, especially through microglial and astrocyte activation. In model systems, it also regulates changes in T-cells. This review focuses on the key findings that have advanced our understanding of the role of ApoE in the pathogenesis of AD and the current view of innate immune response regulated by ApoE in AD, while discussing open questions and areas for future research.

Metagenomic insights into inhibition of soil microbial carbon metabolism by phosphorus limitation during vegetation succession

Abstract There is growing awareness of the need for regenerative practices in the fight against biodiversity loss and climate change. Yet, we lack a mechanistic understanding of how microbial community composition and functioning are likely to change alongside transition from high-density tillage to large-scale vegetation restoration. Here, we investigated the functional dynamics of microbial communities following a complete vegetation successional chronosequence in a subtropical zone, Southwestern China, using shotgun metagenomics approaches. The contents of total soil phosphorus (P), available P, litter P, and microbial biomass P decreased significantly during vegetation succession indicating that P is the most critical limiting nutrient. The abundance of genes related to P-uptake and transport, inorganic P-solubilization, organic P-mineralization, and P-starvation response regulation significantly increased with successional time, indicating an increased microbial “mining” for P under P limitation. Multi-analysis demonstrated microbial P limitation strongly inhibits carbon (C) catabolism potential, resulting in a significant decrease in CAZyme family gene abundances. Nevertheless, over successional time, microorganisms increased investment in genes involved in degradation-resistant compounds (lignin and its aromatic compounds) to acquire P resources in the litter. Our study provides functional gene-level insights into how P limitation during vegetation succession in subtropical regions inhibits soil microbial C metabolic processes, thereby advancing our understanding of belowground C cycling and microbial metabolic feedback during forest restoration.

Metabolite profiling and transcriptome analyses reveal defense regulatory network against pink tea mite invasion in tea plant

BackgroundThe tea plant Camellia sinensis (L.) O. Kuntze is a perennial crop, invaded by diversity of insect pest species, and pink tea mite is one of the most devastating pests for sustainable tea production. However, molecular mechanism of defense responses against pink tea mites in tea is still unknown. In this study, metabolomics and transcriptome profiles of susceptible and resistant tea varieties were compared before and after pink tea mite infestation.ResultsMetabolomics analysis revealed that abundance levels of polyphenol-related compounds changed significantly before and after infestation. At the transcript level, nearly 8 GB of clean reads were obtained from each sequenced library, and a comparison of infested plants of resistant and susceptible tea varieties revealed 9402 genes with significant differential expression. An array of genes enriched in plant pathogen interaction and biosynthetic pathways of phenylpropanoids showed significant differential regulation in response to pink tea mite invasion. In particular, the functional network linkage of disease resistant proteins, phenylalanine ammonia lyase, flavanone -3-hydroxylase, hydroxycinnamoyl-CoA shikimate transferase, brassinosteroid-6-oxidase 1, and gibberellin 2 beta-dioxygenase induced dynamic defense signals to suppress prolonged pink tea mite attacks. Further integrated analyses identified a complex network of transcripts and metabolites interlinked with precursors of various flavonoids that are likely modulate resistance against to pink tea mite.ConclusionsOur results characterized the profiles of insect induced metabolic and transcript reprogramming and identified a defense regulatory network that can potentially be used to fend off pink tea mites damage.

Activation of ATF3 via the integrated stress response pathway regulates innate immune response to restrict Zika virus.

Zika virus (ZIKV) is a re-emerging mosquito-borne flavivirus that co-opts cellular mechanisms to support viral processes that can reprogram the host transcriptional profile. Such viral-directed transcriptional changes and the pro- or anti-viral outcomes remain understudied. We previously showed that ATF3, a stress-induced transcription factor, is significantly upregulated in ZIKV-infected mammalian cells, along with other cellular and immune response genes. We now define the intracellular pathway responsible for ATF3 activation and elucidate the impact of ATF3 expression on ZIKV infection. We show that during ZIKV infection, the integrated stress response pathway stimulates ATF3 which enhances the innate immune response to antagonize ZIKV infection. This study establishes a link between viral-induced stress response and transcriptional regulation of host defense pathways and thus expands our knowledge of virus-mediated transcriptional mechanisms and transcriptional control of interferon-stimulated genes during ZIKV infection.

Gene Expression Profiling and Immune Pathway Dysregulation in Ribonucleoprotein Autoantibody-Positive Systemic Lupus Erythematosus Patients

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation and chronic inflammation across various organ systems. While anti-dsDNA and anti-Sm antibodies are commonly associated with SLE, the presence of anti-RNP antibodies is often linked to unique gene expression profiles and immune responses. This study aims to investigate the gene expression profiles in ribonucleoprotein (RNP) autoantibody-positive SLE patients by analyzing publicly available transcriptomic data. Methods: This study analyzed transcriptomic data from the GEO dataset GSE61635, which includes gene expression profiles from 79 anti-RNP-positive SLE patients and 30 healthy controls. Differentially expressed genes (DEGs) were identified using the GEO2R tool with a p-value < 0.05 and |log2fold change| > 1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Tissue-specific and cell-type enrichment analyses highlighted the involvement of immune tissues. Results: A total of 1891 DEGs were identified between anti-RNP-positive SLE patients and healthy controls. Among the identified DEGs, SLC4A1 and EPB42 were notably downregulated, while PIP4K2A was highly upregulated. Enrichment analyses revealed significant dysregulation in antiviral response and immune regulation pathways. PPI network analysis highlighted key hub genes, suggesting a heightened antiviral state in these patients. Tissue-specific enrichment and cell-type enrichment identified the bone marrow and immune tissues as being highly affected by the altered gene expression. Additionally, gene frequency analysis highlighted RASD2 as being recurrently significant across multiple studies. Conclusions: The findings suggest that anti-RNP-positive SLE patients exhibit distinct gene expression and immune dysregulation profiles, particularly in antiviral and immune regulation pathways. These results provide insights into the molecular mechanisms driving SLE in this patient subset and may guide future therapeutic interventions.

Deep phenotyping reveals CRH and FKBP51-dependent behavioral profiles following chronic social stress exposure in male mice.

The co-chaperone FKBP51, encoded by FKBP5 gene, is recognized as a psychiatric risk factor for anxiety and depressive disorders due to its crucial role in the stress response. Another key modulator in stress response regulation is the corticotropin releasing hormone (CRH), which is co-expressed with FKBP51 in many stress-relevant brain-regions and cell-types. Together, they intricately influence the balance of the hypothalamic-pituitary-adrenal (HPA) axis, one of the primary stress response systems. Previous research underscores the potential moderating effects these genes have on the regulation of the stressful life events towards the vulnerability of major depressive disorder (MDD). However, the specific function of FKBP51 in CRH-expressing neurons remains largely unexplored. Here, through deep behavioral phenotyping, we reveal heightened stress effects in mice lacking FKBP51 in CRH co-expressing neurons (CRHFKBP5-/-), particularly evident in social contexts. Our findings highlight the importance of considering cell-type specificity and context in comprehending stress responses and advocate for the utilization of machine-learning-driven phenotyping of mouse models. By elucidating these intricacies, we lay down the groundwork for personalized interventions aimed at enhancing stress resilience and individual well-being.

NH4Cl-induced metabolic acidosis increases the abundance of HCO3− transporters in the choroid plexus of mice

Regulation of cerebrospinal fluid (CSF) pH and brain pH are vital for all brain cells. The acute regulation of CSF pH is dependent on the transport of HCO3− across the choroid plexus in the brain ventricles. Acute regulation in response to acidosis is dependent on H+ export and HCO3− import across the plasma membrane. Acute regulation in response to alkalosis is dependent on HCO3− export across the plasma membrane. The objective of the study was to investigate the contribution of the Na+-dependent HCO3− transporters, Ncbe, NBCn1, and NBCe2 to CSF pH regulation during chronic metabolic acidosis in mice. To induce metabolic acidosis, mice received 0.28 M ammonium chloride (NH4Cl) in the drinking water for three, five, or seven days. While in vivo, CSF pH measurements did not differ, measurements of CSF [HCO3−] revealed a significantly lower CSF [HCO3−] after three days of acid-loading. Immunoblotting of choroid plexus protein samples showed that the abundance of the basolateral Na+/HCO3− transporter, NBCn1, was significantly increased. This was followed by a significant increase in CSF secretion rate determined by ventriculo-cisternal perfusion. After five days of treatment with NH4Cl, CSF [HCO3−] levels were normalized. After the normalization of CSF [HCO3−], CSF secretion was no longer increased but the abundance of the basolateral Na+-dependent HCO3− transporters Ncbe and NBCn1 increased. The luminal HCO3− transporter, NBCe2, was unaffected by the treatment. In conclusion, we establish that 1) acidotic conditions increase the abundance of the basolateral Na+-dependent HCO3− transporters in the choroid plexus, 2) NH4Cl loading in mice lowers CSF [HCO3−] and 3) leads to increased CSF secretion likely caused by the increased capacity for transepithelial transport of Na+ and HCO3− in the choroid plexus.

Sexual Victimization History and Emotion Regulation in Daily Life: A Role for Stress Sensitization.

Relative to other types of traumatic experiences, a lifetime history of sexual violence (SV) has been linked with more persistent and severe mental health outcomes, but the reasons for this discrepancy have not been clearly established. Stress sensitization, or the amplification of responses to daily stressors as a function of trauma history, offers one possible explanation. Using ecological momentary assessment, the current study tested stress sensitization effects in daily life for individuals with a history of SV, focusing on emotion regulation as an outcome. Smartphone surveys were delivered four times per day over a 2-week period to assess relationships between prior SV exposure, daily stressors, and emotion regulation in an undergraduate sample (N = 122). As expected, individuals with lifetime exposure to SV evidenced increased emotion dysregulation and maladaptive emotion regulation in response to daily stressors relative to nonexposed peers, even after accounting for cumulative trauma. However, the SV and non-SV groups did not differ significantly on state adaptive emotion regulation. Instead, experiencing daily stressors was associated with increased adaptive emotion regulation for individuals in both groups. Broadly, results suggest that SV is uniquely associated with increased sensitivity to daily stressors, manifested as emotion dysregulation and use of maladaptive emotion regulation strategies to regulate emotions. These findings are consistent with emerging research on the neurobiology of trauma and with an emphasis on emotion regulation skills in leading interventions for SV-exposed individuals. Stress sensitization warrants additional attention as a factor linking SV and mental health problems.

Assessment of toxicity changes induced by exposure of human cells to lunar dust simulant

The toxicity of lunar dust (LD) to astronauts' health has been confirmed in the Apollo missions and subsequent biological experiments. Therefore, it is crucial to understand the biological toxicity of lunar dust for future human missions to the Moon. In this study, we exposed human lung epithelial cells (BEAS-2B) and peripheral blood B lymphocytes (AHH-1) to varying concentrations (0, 500, 1000, and 1500 μg/ml) of a lunar dust simulant (LDS) called CLDS-i for 24 and 48 h. The results provided the following key findings: (1) LDS induction of cell damage occurred through oxidative stress, with the levels of reactive oxygen species (ROS) in BEAS-2B cells being dependent on the duration of exposure. (2) Necrosis and early apoptosis were observed in BEAS-2B cells and AHH-1 cells, respectively. In addition, both cells showed lysosomal damage. (3) Genes CXCL1, SPP1, CSF2, MMP1, and POSTN are implicated in immune response and cytoskeletal arrangement regulation in BEAS-2B cells. Considering the similarities in composition and properties between CLDS-i and real lunar dust, our findings not only enhance the understanding of LDS toxicity, but also contribute to a better comprehension of the genomic alterations and molecular mechanisms underlying cellular toxicity induced by LD. These insights will contribute to the development of a biotoxicology framework aimed at safeguarding the health of astronauts and, consequently, facilitating future human missions to the Moon.

Taxonomic Diversity, Predicted Metabolic Pathway, and Interaction Pattern of Bacterial Community in Sea Urchin Anthocidaris crassispina.

Bacterial assemblages associated with sea urchin are critical to their physiology and ecology within marine ecosystems. In this study, we characterized the bacterial communities in wild sea urchin Anthocidaris crassispina captured in Daya Bay, South China Sea. A total of 363 amplicon sequence variants belonging to nine phyla and 141 genera were classified from intestine, body surface, and surrounding seawater samples. Proteobacteria, Firmicutes, and Bacteroidetes were the dominant bacteria phyla found in this study. A network analysis of bacterial interspecies interactions revealed varying complexity, stability, connectivity, and relationship patterns across the samples, with the most intricate network observed in the surrounding seawater. Metagenomic predictions highlighted the distinct bacterial metabolic pathways, with significant differences between intestine and seawater samples. Notably, pathways associated with polysaccharide degradation, including chitin derivatives, starch, and CoM biosynthesis, were markedly abundant, underscoring the gut microbiota's key role in digesting algae. In addition, other metabolic pathways in intestine samples were linked to immune response regulation of sea urchins. Overall, this study provides a comprehensive overview of the bacterial community structure and potential functional roles in A. crassispina.

Novice EFL Teachers’ Belief and Emotional Regulation in Response to Students’ Misbehaviors in the Classrooms

This research report shares the findings that emerged from a qualitative study in which the main objective was to discover whether or not novice EFL teachers regulate their negative emotions during their initial teaching practice and, if so, how they do this. Semi-structured interviews, recorded classroom observations, collected the data, stimulated recall interviews, and wrote journals for reflections and explanations of why they expressed and regulated their emotions in those incidents. The participants were three novice teachers who have been teaching English at the same university for about five years. Data collection of student-teacher interaction was carried out during their teaching. The research findings reveal that teachers often experience negative emotions triggered by students' conduct in the classroom, such as discipline issues, lack of engagement, and incorrect responses. Teachers successfully used techniques to redirect their attention and reassess the situation to counteract annoyance and disappointment. Ultimately, these strategies replaced negative emotions with a new outlook through substitute teaching activities. These observations provide EFL teachers with insightful advice on dealing with negative emotions effectively, resulting in a more positive classroom atmosphere where English is taught.

Comprehensive proteomic analysis of buffalo milk extracellular vesicles

Extracellular vesicles are secretory vesicles involved in cell-to-cell communication via their encapsulated cargo of proteins, lipids, and nucleic acids. Bovine milk provides a rich source of extracellular vesicles (mEVs) that have been studied as therapeutics and drug delivery systems. Therefore, insight into the mEV cargo, such as its proteome, may help in understanding the molecular mechanism underlying the potential health benefits attributed to the mEVs. Hence, mEVs were isolated from healthy buffalo milk after screening the milk somatic cell count. The total proteins of mEVs were analyzed using LC-MS, and 331 proteins were found commonly present among three buffalo milk samples. These proteins were primarily derived from extracellular regions and lysosomes. The major biological roles associated with the proteins were immune response, metabolism, and cell cycle regulation. The molecular functions of the proteins were transporter activity, catalytic activity, and GTPase activity. Further, comparative analysis with the previously available bovine mEVs proteome data showed 114 proteins to be newly identified in the buffalo mEVs. The biological pathways associated with these proteins may play a major role in muscle development. These findings shed a light on the potential health benefits of buffalo mEVs as therapeutics as well as drug delivery vehicles.

Update on Ergonomics Standards in the United States

After two decades of dormancy, activity around ergonomics rulemaking has increased recently, primarily due to legislation passed at the state level. Several states have enacted laws addressing production quotas in warehouses and the impact they have on worker safety and health. Minnesota added an ergonomics program requirement for industries with known risk for work-related musculoskeletal disorders to their safe patient handling and warehouse quota regulations in response to legislation passed in 2023. In that same year, the Washington State Legislature passed laws that resulted in a warehouse quota regulation and initiated industry-specific rulemaking efforts. This paper provides an overview of current ergonomics standards at the state level and offers a national perspective from federal OSHA.

Overexpression of Vitis GRF4-GIF1 improves regeneration efficiency in diploid Fragaria vesca Hawaii 4

BackgroundPlant breeding played a very important role in transforming strawberries from being a niche crop with a small geographical footprint into an economically important crop grown across the planet. But even modern marker assisted breeding takes a considerable amount of time, over multiple plant generations, to produce a plant with desirable traits. As a quicker alternative, plants with desirable traits can be raised through tissue culture by doing precise genetic manipulations. Overexpression of morphogenic regulators previously known for meristem development, the transcription factors Growth-Regulating Factors (GRFs) and the GRF-Interacting Factors (GIFs), provided an efficient strategy for easier regeneration and transformation in multiple crops.ResultsWe present here a comprehensive protocol for the diploid strawberry Fragaria vesca Hawaii 4 (strawberry) regeneration and transformation under control condition as compared to ectopic expression of different GRF4-GIF1 chimeras from different plant species. We report that ectopic expression of Vitis vinifera VvGRF4-GIF1 provides significantly higher regeneration efficiency during re-transformation over wild-type plants. On the other hand, deregulated expression of miRNA resistant version of VvGRF4-GIF1 or Triticum aestivum (wheat) TaGRF4-GIF1 resulted in abnormalities. Transcriptomic analysis between the different chimeric GRF4-GIF1 lines indicate that differential expression of FvExpansin might be responsible for the observed pleiotropic effects. Similarly, cytokinin dehydrogenase/oxygenase and cytokinin responsive response regulators also showed differential expression indicating GRF4-GIF1 pathway playing important role in controlling cytokinin homeostasis.ConclusionOur data indicate that ectopic expression of Vitis vinifera VvGRF4-GIF1 chimera can provide significant advantage over wild-type plants during strawberry regeneration without producing any pleiotropic effects seen for the miRNA resistant VvGRF4-GIF1 or TaGRF4-GIF1.

Structural basis of nucleic acid recognition by the N-terminal cold shock domain of the plant glycine-rich protein AtGRP2.

AtGRP2 is a glycine-rich, RNA-binding protein that plays pivotal roles in abiotic stress response and flowering time regulation in Arabidopsis thaliana. AtGRP2 consists of an N-terminal cold shock domain (CSD) and two C-terminal CCHC-type zinc knuckles interspersed with glycine-rich regions. Here, we investigated the structure, dynamics, and nucleic acid binding properties of AtGRP2-CSD. The 2D [1H,15N] HSQC spectrum of AtGRP2-CSD1-79 revealed the presence of a partially folded intermediate in equilibrium with the folded state. The addition of eleven residues at the C-terminus stabilized the folded conformation. The three-dimensional structure of AtGRP2-CSD1-90 unveiled a β-barrel composed of five antiparallel β-strands and a 310 helical turn, along with an ordered C-terminal extension, a conserved feature in eukaryotic CSDs. Direct contacts between the C-terminal extension and the β3-β4 loop further stabilized the CSD fold. AtGRP2-CSD1-90 exhibited nucleic acid binding via solvent-exposed residues on strands β2 and β3, as well as the β3-β4 loop, with higher affinity for DNA over RNA, particularly favoring pyrimidine-rich sequences. Furthermore, DNA binding induced rigidity in the β3-β4 loop, evidenced by 15N-{1H} NOE values. Mutation of residues W17, F26, and F37, in the central β-sheet, completely abolished DNA binding, highlighting the significance of π-stacking interactions in the binding mechanism. These results shed light on the mechanism of nucleic acid recognition employed by AtGRP2, creating a framework for the development of biotechnological strategies aimed at enhancing plant resistance to abiotic stresses.

Elucidating the Role of Autophagy-related Genes in Polycystic Ovary Syndrome: Implications for Diagnostic Models and Immune Response Regulation.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder that negatively affects female reproductive capacity. Although the association between autophagy and PCOS is known, there are few detailed studies on the association between autophagy-related genes and PCOS. Publicly available gene expression datasets (GSE102293, GSE138518, GSE34526, GSE114419, GSE137684, GSE155489) were used in a comprehensive analysis to identify a role for autophagy in PCOS. Batch effects were mitigated using the sva package, followed by WGCNA (weighted gene correlation network analysis) and ss- GSEA (single sample gene set enrichment analysis) to identify autophagy-related genes. Recursive feature elimination (RFE) and LASSO COX methods were used to identify important hub genes, and their correlation with immune cell activity was assessed using ssGSEA and Pearson correlation analysis. High autophagy scores were observed in PCOS samples, and the dark green gene module with the highest autophagy correlation was identified. The differential analysis identified a total of 169 up-regulated genes versus 2 down-regulated genes in the PCOS samples, which were intersected by taking the intersection with the deep green module genes and resulted in 121 key genes. Subsequently, 6 hub genes (MMP25, CSF3R, SLPI, MMP9, CLEC4E, and SIGLEC10) were further identified based on RFE and LASSO algorithms. Diagnostic efficacy based on ROC curves showed six autophagy- associated hub genes with AUC values as high as 0.959 and 0.896 in the training and validation sets, respectively. Finally, we observed that these hub genes are strongly associated with immune function, especially chronic inflammation and aberrant immune activation pathways. In this study, we identified autophagy genes closely related to PCOS and constructed a gene model with high diagnostic accuracy. These findings not only provided potential new biomarkers for the diagnosis of PCOS but also revealed the key role of autophagy in the pathogenesis of PCOS.

Genetic Profiling in Chronic Lymphocytic Leukemia: The Role of TP53 Mutations and IGHV Status in Treatment Decision-Making – A Case Report

Introduction. The TP53 gene encodes the p53 protein, crucial for DNA damage response, apoptosis, and cell cycle regulation. In chronic lymphocytic leukemia (CLL), TP53 loss due to 17p deletion or mutation leads to poor chemoimmunotherapy response and shorter survival. Patients with unmutated immunoglobulin heavy chain variable (IGHV) status exhibit a more aggressive disease course, poorer outcomes, and reduced response to standard chemoimmunotherapy. These genetic variations significantly affect disease progression, treatment choice, and response to therapy. Case Report. In November 2023, a 61-year-old man presented to our clinic with complaints of generalized weakness and rapid fatigue since October 2023. CLL was diagnosed in 2018 through pathohistological and immunohistochemical analysis of the bone marrow. The patient received no therapy until 2023 due to the absence of active disease signs. From March 28, 2023, to July 25, 2023, the patient received chemoimmunotherapy with the bendamustine and rituximab (BR) regimen. Five courses of therapy were administered; however, further treatment was discontinued due to side effects that occurred during the fifth course of bendamustine administration. A subsequent diagnostic evaluation aimed at assessing treatment efficacy, prognosis, and genetic profiling included a cytomorphological analysis, which revealed that lymphocytes comprised 80% of the cellular composition. Immunocytological analysis confirmed the presence of monoclonal atypical lymphocytes, accounting for 70% of the cell population. Next-generation sequencing identified a pathogenic TP53 mutation, and fragment analysis confirmed an unmutated IGHV status. The presence of the TP53 mutation and unmutated IGHV status categorizes the patient as being in the very high-risk group, for which the use of Bruton’s tyrosine kinase inhibitors (BTKIs) and/or B-cell lymphoma-2 (BCL-2) inhibitors is recommended. Conclusions. This case highlights the significance of comprehensive genetic profiling in CLL patients using techniques such as fluorescence in situ hybridization, polymerase chain reaction, and next-generation sequencing. Such profiling detects molecular genetic alterations, facilitating personalized and effective treatment.

MCTP controls nucleocytoplasmic partitioning of AUXIN RESPONSE FACTORs during lateral root development.

The plant hormone auxin orchestrates almost all aspects of plant growth and development. AUXIN RESPONSE FACTORs (ARFs) control the transcription of auxin-responsive genes, forming cytoplasmic condensates to modulate auxin sensitivity and diversify auxin response regulation. However, the dynamic control of ARF distribution across different subcellular compartments remains largely obscure. Here, we show that three MULTIPLE C2 DOMAIN AND TRANSMEMBRANE REGION PROTEINs (MCTPs), MCTP3, MCTP4, and MCTP6, control ARF nucleocytoplasmic partitioning and determine lateral root development. MCTP3/4/6 are highly expressed in lateral roots and specifically interact with ARF7 and ARF19 to dissolve their cytoplasmic condensates. This promotes ARF nuclear localization in lateral root primordia and enhances auxin signaling during lateral root formation. Our findings confer MCTP as a key switch to modulate auxin responses and outline an MCTP-ARF signaling cascade that is crucial for the establishment of the plant root system.