Differential Patterns Research Articles

The biogeographic patterns of the olive fly and its primary symbiont Candidatus Erwinia dacicola across the distribution area of the olive tree.

The olive fly, Bactrocera oleae (Rossi, 1790), is the major insect pest of olives attacking both cultivated and wild olive. Bactrocera oleae carries a primary and vertically transmitted symbiont, the bacterium Candidatus Erwinia dacicola. As any primary symbiont, it plays an important role in the reproduction and lifespan of the fly. The genetic 16S rRNA diversity of the primary symbiont and the mitochondrial haplotype variation of the insect host were simultaneously examined in 54 olive fly populations. The aim was to unravel the biogeographic patterns of this economically relevant host-bacteria interaction across a wide distribution area. Three symbiont haplotypes were identified. The primary symbiont showed a lower haplotype diversity than that of its host, a characteristic indicative of a long-term interaction. A significant genetic and geographic association between host and primary symbiont was observed, with an East-West genetic differentiation pattern in the Mediterranean basin, coinciding with the historical genetic distribution of the olive tree. The study shows promise, informing and aiding the development of future tools for the control of the olive fly.

Effects of Cognition-based and Affect-based Trust Attitudes on Trust Intentions

Despite decades of research on trust in the workplace, researchers continue to struggle with fundamental questions regarding the conceptualization and measurement of organizational trust. To help clarify this construct, we revisit established trust definitions (Mayer et al. Academy of Management Review, 20(3), 709–734, Mayer et al., Academy of Management Review 20:709–734, 1995; Rousseau et al. Academy of Management Review, 23(3), 393–404, Rousseau et al., Academy of Management Review 23:393–404, 1998) and distinguish trust attitudes (i.e., positive expectations of others) from trust intentions (i.e., the willingness to be vulnerable). Using a three-study experimental design, we examined the causal effect of two distinct trust attitudes (i.e., cognition-based and affect-based) on two trust intentions (i.e., reliance and disclosure). We found that when cognition-based trust was high, participants were more willing to rely on a colleague (i.e., had higher reliance intentions). When affect-based trust was high, participants were more willing to share sensitive information with that colleague (i.e., higher disclosure intentions) and more willing to rely on a colleague (i.e., higher reliance intentions). We also examined the effect of mixed trust attitudes (i.e., feelings of low (vs. high) cognition-based trust paired with high (vs. low) affect-based trust). We found that, for reliance intentions, for the most part, high affect-based trust could be substituted with high cognition-based trust. Conversely, for disclosure intentions, high cognition-based trust could not substitute for high affect-based trust. The observed patterns indicate that affect-based and cognition-based attitudes are related yet distinct, with differential patterns of prediction with reliance and disclosure intentions. Our findings also underscore the importance of affect-based trust. By nurturing strong interpersonal bonds among employees, organizations can improve communication and collaboration, critical elements for organizational effectiveness.

Unveiling the glycolysis in sepsis: Integrated bioinformatics and machine learning analysis identifies crucial roles for IER3, DSC2, and PPARG in disease pathogenesis.

Sepsis, a multifaceted syndrome driven by an imbalanced host response to infection, remains a significant medical challenge. At its core lies the pivotal role of glycolysis, orchestrating immune responses especially in severe sepsis. The intertwined dynamics between glycolysis, sepsis, and immunity, however, have gaps in knowledge with several Crucial genes still shrouded in ambiguity. We harvested transcriptomic profiles from the peripheral blood of 107 septic patients juxtaposed against 29 healthy controls. Delving into this dataset, differential expression analysis shed light on genes distinctly linked to glycolysis in both cohorts. Harnessing the prowess of LASSO regression and SVM-RFE, we isolated Crucial genes, paving the way for a sepsis risk prediction model, subsequently vetted via Calibration and decision curve analysis. Using the CIBERSORT algorithm, we further mapped 22 immune cell subtypes within the septic samples, establishing potential interactions with the delineated Crucial genes. Our efforts unveiled 21 genes intricately tied to glycolysis that exhibited differential expression patterns. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses offered insights, spotlighting pathways predominantly associated with oxidative phosphorylation, PPAR signaling pathway, Glycolysis/Gluconeogenesis and HIF-1 signaling pathway. Among the myriad genes, IER3, DSC2, and PPARG emerged as linchpins, their prominence in sepsis further validated through ROC analytics. These sentinel genes demonstrated profound affiliations with various immune cell facets, bridging the complex terrain of glycolysis, sepsis, and immune responses. In line with our endeavor to "unveil the glycolysis in sepsis," the discovery of IER3, DSC2, and PPARG reinforces their cardinal roles in sepsis pathogenesis. These revelations accentuate the intricate dance between glycolysis and immunological shifts in septic conditions, offering novel avenues for therapeutic interventions.

Distinct connectivity patterns in bipolar and unipolar depression: a functional connectivity multivariate pattern analysis study

BackgroundPatients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD.MethodologyIn a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls.ResultsFC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG.ConclusionsDifferences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.

Interplay of RNA m6A Modification-Related Geneset in Pan-Cancer.

Background: N6-methyladenosine (m6A), is the most common modification found in mRNA and lncRNA in higher organisms and plays an important role in physiology and pathology. However, its role in pan-cancer has not been explored. Results: A total of 31 m6A modification regulators, including 12 writers, 2 erasers, and 17 readers are identified in the current study. The functional analysis of the regulators results in the enrichment of processes, primarily related to RNA modification and metabolism, and the PPI network reveals multiple interactions among the regulators. The mRNA expression analysis reveals a high expression for most of the regulators in pan-cancer. Most of the m6A regulators are found to be mutated across the cancers, with ZC3H13, VIRMA, and PRRC2A having a higher frequency rate. Significant correlations of the regulators with clinicopathological parameters, such as age, gender, tumor stage, and grade are identified in pan-cancer. The m6A regulators' expression is found to have significant positive correlations with the miRNAs in pan-cancer. The expression pattern of the m6A regulators is able to classify the tumors into different subclusters as well as into high- and low-risk groups. These tumor groups show differential patterns in terms of their immune cell infiltration, tumor stemness score, genomic heterogeneity score, expression of immune regulatory/checkpoint genes, and correlations between the regulators and the drugs. Conclusions: Our study provide a comprehensive overview of the functional roles, genetic and epigenetic alterations, and prognostic value of the RNA m6A regulators in pan-cancer.

Updated annotation and meta-analysis of Brugia malayi transcriptomics data reveals consistent transcriptional profiles across time and space with some study-specific differences in adult female worm transcriptional profiles.

Genomics, transcriptomics, and proteomics have significantly advanced our understanding of obligately host-associated microbes, where interrogation of the biology is often limited by the complexity of the biological system and limited tools. This includes the causative agents of many neglected tropical diseases, including filarial nematodes. Therefore, numerous transcriptomics studies have been undertaken on filarial nematodes. Most of these transcriptomics studies focus on Brugia malayi, which causes lymphatic filariasis and is a laboratory model for human filarial disease. Here, we undertook a meta-analysis of the publicly available B. malayi transcriptomics data enabling the direct cross comparison of samples from almost a dozen studies. This reanalysis highlights the consistency of transcriptomics results across many different studies and experimental designs from across the globe for over a decade of research, across many different generations of a sequencing technology, library preparation protocols, and differential expression tools. Males and microfilariae across samples had similar expression profiles. However, female samples were clustered into two differential expression patterns that were significantly different from one another. Largely, we confirm previous results for all studies reanalyzed including tissue-specific gene expression and anti-Wolbachia doxycycline treatment of microfilaria. However, we did not detect previously reported differential expression upon in vitro or in vivo treatment with ivermectin, albendazole, and DEC, instead identifying a consistent lack of transcriptomic change upon exposure to these anthelminthic drugs. Updated annotation has been provided that denotes poorly supported genes including those overlapping rRNAs.

Community-Supported Shared Infrastructure in Support of Speech Accessibility.

The Speech Accessibility Project (SAP) intends to facilitate research and development in automatic speech recognition (ASR) and other machine learning tasks for people with speech disabilities. The purpose of this article is to introduce this project as a resource for researchers, including baseline analysis of the first released data package. The project aims to facilitate ASR research by collecting, curating, and distributing transcribed U.S. English speech from people with speech and/or language disabilities. Participants record speech from their place of residence by connecting their personal computer, cell phone, and assistive devices, if needed, to the SAP web portal. All samples are manually transcribed, and 30 per participant are annotated using differential diagnostic pattern dimensions. For purposes of ASR experiments, the participants have been randomly assigned to a training set, a development set for controlled testing of a trained ASR, and a test set to evaluate ASR error rate. The SAP 2023-10-05 Data Package contains the speech of 211 people with dysarthria as a correlate of Parkinson's disease, and the associated test set contains 42 additional speakers. A baseline ASR, with a word error rate of 3.4% for typical speakers, transcribes test speech with a word error rate of 36.3%. Fine-tuning reduces the word error rate to 23.7%. Preliminary findings suggest that a large corpus of dysarthric and dysphonic speech has the potential to significantly improve speech technology for people with disabilities. By providing these data to researchers, the SAP intends to significantly accelerate research into accessible speech technology. https://doi.org/10.23641/asha.27078079.

Clustering-independent estimation of cell abundances in bulk tissues using single-cell RNA-seq data.

Single-cell RNA-sequencing has transformed the study of biological tissues by enabling transcriptomic characterizations of their constituent cell states. Computational methods for gene expression deconvolution use this information to infer the cell composition of related tissues profiled at the bulk level. However, current deconvolution methods are restricted to discrete cell types and have limited power to make inferences about continuous cellular processes like cell differentiation or immune cell activation. We present ConDecon, a clustering-independent method for inferring the likelihood for each cell in a single-cell dataset to be present in a bulk tissue. ConDecon represents an improvement in phenotypic resolution and functionality with respect to regression-based methods. Using ConDecon, we discover the implication of neurodegenerative microglia inflammatory pathways in the mesenchymal transformation of pediatric ependymoma and characterize their spatial trajectories of activation. The generality of this approach enables the deconvolution of other data modalities such as bulk ATAC-seq data.

Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma

Glioblastoma is characterized by a pronounced resistance to therapy with dismal prognosis. Transcriptomics classify glioblastoma into proneural (PN), mesenchymal (MES) and classical (CL) subtypes that show differential resistance to targeted therapies. The aim of this study was to provide a viable approach for identifying combination therapies in glioblastoma subtypes. Proteomics and phosphoproteomics were performed on dasatinib inhibited glioblastoma stem cells (GSCs) and complemented by an shRNA loss-of-function screen to identify genes whose knockdown sensitizes GSCs to dasatinib. Proteomics and screen data were computationally integrated with transcriptomic data using the SamNet 2.0 algorithm for network flow learning to reveal potential combination therapies in PN GSCs. In vitro viability assays and tumor spheroid models were used to verify the synergy of identified therapy. Further in vitro and TCGA RNA-Seq data analyses were utilized to provide a mechanistic explanation of these effects. Integration of data revealed the cell cycle protein WEE1 as a potential combination therapy target for PN GSCs. Validation experiments showed a robust synergistic effect through combination of dasatinib and the WEE1 inhibitor, MK-1775, in PN GSCs. Combined inhibition using dasatinib and MK-1775 propagated DNA damage in PN GCSs, with GCSs showing a differential subtype-driven pattern of expression of cell cycle genes in TCGA RNA-Seq data. The integration of proteomics, loss-of-function screens and transcriptomics confirmed WEE1 as a target for combination with dasatinib against PN GSCs. Utilizing this integrative approach could be of interest for studying resistance mechanisms and revealing combination therapy targets in further tumor entities.

Rho4 interacts with BbGDI and is essential for the biocontrol potential of Beauveria bassiana by maintaining intracellular redox homeostasis

Rho4 is a member of the Rho-family small GTPases. In this study, we revealed the function of Rho4 and explored its mechanism involved in intracellular redox homeostasis in Beauveria bassiana, one of the most widely utilized filamentous entomopathogenic fungi. The disruption of Rho4 in B. bassiana resulted in significant phenotypic changes, such as fungal virulence, growth rate on different media, thermotolerance, germination, and conidiation. Integrated analysis of proteomic and transcriptomic data unveiled differential expression patterns of various redox-related genes and proteins in Δrho4, including the down-regulation of GST shown in proteomic and transcriptomic data, and the down-regulated gene expression levels of NOX, SOD, CAT, and GR in the transcriptome. Based on the bi-omics analysis, we focused on the impact of Rho4 in maintaining intracellular redox homeostasis. A decreased ROS content observed in Δrho4 might be attributed to the reduced NOX activity, which subsequently affects the GSH-producing/consuming metabolisms, with the attenuated activities of GR and GST. The imbalanced redox homeostasis also resulted in the reduced enzyme activities of SOD and CAT. Exogenous oxides could partially complement the ROS level and rescue the growth defect in Δrho4 to a certain extent. Besides, BbGDI was initially identified as an interacting protein of Rho4 in entomopathogenic fungi. Our results provide a comprehensive understanding of the function and regulating mechanism of Rho4 in B. bassiana.

Mechanistic Regulation of Epidermal Growth Factor and Hormonal Receptors by Kinase Inhibitors and Organofluorines in Breast Cancer Therapy.

Differential expression patterns of growth factor (EGFR, HER-2) and hormonal (ER, PR) receptors in breast cancer (BC) remain crucial for evaluating and tailoring therapeutic interventions. This study investigates differential expression profiles of hormonal and growth factor receptors in BC patients and across age groups, major subclasses, disease stages and tumor histology and survival rates, the efficacy of emerging clinical trial drugs (Dabrafenib and Palbociclib) and elucidating their molecular interaction mechanisms for efficient therapeutic strategies. Gene and protein expression analysis in the normal vs BC and across age groups and major subclasses reveals divergent patterns as EGFR and HER-2 levels are reduced in tumors versus normal tissue, while ER and PR levels are higher, particularly in luminal subtypes. However, there was no significant difference in survival rates among high and low/medium expression levels of EGFR and PR receptors. Conversely, patients with high HER-2 and ER expression exhibited poorer survival rates compared to low or medium expression levels. The in vitro findings indicate that Dabrafenib exhibits greater effectiveness than Palbociclib in suppressing various BC cells such as MCF-7 (Luminal), MDA-MB-231 (Triple-Negative), SKBR-3 (HER-2 + ) proliferation, promoting cell death, (IC50 of Dab < Pal) at 24 and 48 h, ROS production, and reduced ER and PR, elevated HER-2 with no change in EGFR expression. Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.

Short-Term Growth Dynamics of Spontaneous and Planted Vegetation on Subtropical Extensive Green Roof as Renaturalized Biotope

Spontaneous vegetation within a managed green space is often regarded as unwelcoming and insignificant weeds. This perception is still deep-rooted among green-space managers and the general public worldwide; they are generally uncertain about the management needs after allowing these groups of flora to take root. The short-term growth dynamics of both spontaneous and planted vegetation should be analyzed, and a widely acceptable, feasible management plan to balance aesthetic and ecological functions should be formulated with the backing of data and analysis for such fast-growing flora in tropical and subtropical regions. A manicured, extensive green roof with only seven (two native, five exotic) plant species was transformed into a renaturalized biotope by replacing 15 native ferns and forb species over 15 months. After planting, a baseline plant survey was conducted, with 54 plant species representing spontaneous growth and 14 planted species alive (7 planted native species survived, plus 7 species planted prior to renaturalization revived). Three quarterly plant surveys recorded the cover-abundance of each species, and the growth dynamics of the planted and spontaneous plant species were evaluated over the first year of study. During each quarterly survey, the number of planted and spontaneous plant species remained stable (ranging from 14 to 16 species and 51 to 54 species, respectively), with a constant turnover of 11 to 12 die-out species and 11 to 12 newly colonized or revived species. Plant coverage of different plant forms fluctuated slightly (within 7%) in the quarterly surveys according to seasonal changes, except for ferns, which outperformed (12% increase in coverage in a year) all the other plant forms. The height of the planted vegetation fluctuated in a year, being shorter during the summer, while the height of spontaneous vegetation remained stable throughout the year, exhibiting resilience to scouring heat. The seasonal growth tendencies of both planted and spontaneous plants were illustrated in relation to their species ranks, and further hierarchical cluster analysis was conducted for the clustering of spontaneous species. Their differential growth patterns provided comprehensive information or supported decisions regarding plant selection and maintenance, which is a scientific novelty within this unexplored topic. Management recommendations based on the findings were suggested to fulfill both aesthetic and ecological needs. Species with stable and less stable growth patterns could be useful to meet maintenance efficiency and biodiversity enhancement needs, respectively. These findings provide insights to form guiding principles for choosing plant species for renaturalization projects.

Genetic Variations in the NRF2 Microsatellite Contribute to the Regulation of Bovine Sperm-Borne Antioxidant Capacity.

Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor protein-coding gene, considered a master regulator of the cellular stress response. The genetic variations of the NRF2 could influence its transcriptional profile and, subsequently, the stress resilience in all cell types, including sperm cells. Therefore, the sperm-borne antioxidants abundance in association with the genetic variation of a GCC microsatellite located at the 5' upstream region of the NRF2 gene was investigated in young (n = 8) and old (n = 8) Holstein bulls' sperm cells at different seasons. The sperm DNA was sequenced using Sanger sequencing, while- the sperm-borne mRNA analysis was carried out using the synthesized cDNA and qPCR. The data were statistically analyzed using GraphPad Prism 10.0.2 software. The results showed that two bulls had a heterozygous genotype of eight and nine GCC repeats, while biallelic of eight, nine, and fifteen repeats were identified in two, ten, and two bulls, respectively. The computational in silico analysis revealed that the NRF2 upstream sequence with 15, 9, and 8 GCC repeats bound with 725, 709, and 707 DNA-binding transcription factor proteins, respectively. Lower quality of sperm DNA was detected in the spring season compared to other seasons and in young bulls compared to old ones, particularly in the summer and autumn seasons. The mRNA expression analysis revealed that the PRDX1 gene was the abundant transcript among the studied sperm-borne antioxidants and was significantly determined in old bulls' spermatozoa. Moreover, two transcripts of the NRF2 gene and antioxidant (SOD1, CAT, GPX1, TXN1, NQO1) genes displayed differential expression patterns between the age groups across seasons in an antioxidant-dependent manner. The bulls with a heterozygous GCC sequence exhibited elevated sperm-borne mRNA levels of NRF2 and PRDX1 transcripts. Taken together, the findings suggest that the NRF2-GCC microsatellite may contribute to the transcription regulation of NRF2 transcripts and their subsequent downstream antioxidants in bovine sperm cells.

Molecular Characteristics and Expression Patterns of Carotenoid Cleavage Oxygenase Family Genes in Rice (Oryza sativa L.)

Carotenoid cleavage oxygenases (CCOs) cleave carotenoid molecules to produce bioactive products that influence the synthesis of hormones such as abscisic acid (ABA) and strigolactones (SL), which regulate plant growth, development, and stress adaptation. Here, to explore the molecular characteristics of all members of the OsCCO family in rice, fourteen OsCCO family genes were identified in the genome-wide study. The results revealed that the OsCCO family included one OsNCED and four OsCCD subfamilies. The OsCCO family was phylogenetically close to members of the maize ZmCCO family and the Sorghum SbCCO family. A collinearity relationship was observed between OsNCED3 and OsNCED5 in rice, as well as OsCCD7 and OsNCED5 between rice and Arabidopsis, Sorghum, and maize. OsCCD4a and OsCCD7 were the key members in the protein interaction network of the OsCCO family, which was involved in the catabolic processes of carotenoids and terpenoid compounds. miRNAs targeting OsCCO family members were mostly involved in the abiotic stress response, and RNA-seq data further confirmed the molecular properties of OsCCO family genes in response to abiotic stress and hormone induction. qRT-PCR analysis showed the differential expression patterns of OsCCO members across various rice organs. Notably, OsCCD1 showed relatively high expression levels in all organs except for ripening seeds and endosperm. OsNCED2a, OsNCED3, OsCCD1, OsCCD4a, OsCCD7, OsCCD8a, and OsCCD8e were potentially involved in plant growth and differentiation. Meanwhile, OsNCED2a, OsNCED2b, OsNCED5, OsCCD8b, and OsCCD8d were associated with reproductive organ development, flowering, and seed formation. OsNCED3, OsCCD4b, OsCCD4c, OsCCD8b, and OsCCD8c were related to assimilate transport and seed maturation. These findings provide a theoretical basis for further functional analysis of the OsCCO family.

Multifaceted role of microRNA-301a in human cancer: from biomarker potential to therapeutic targeting.

With the growing data on microRNA (miRNA) expression in tissues and circulation, there is increasing evidence for the potential of microRNAs to serve as biomarkers in cancer diagnosis and prognosis, as well as novel therapeutic targets. The expression level of miRNA-301a (miR-301a) is altered in a wide range of human tumor types, and numerous studies have revealed the roles of miR-301a in tumorigenesis and tumor progression. Herein, we comprehensively summarize, compare, and contrast the research advancements on the role of miR-301a in different cancers. Differential expression patterns of miR-301a in tissues and biofluids are implicated in cancer diagnosis, treatment response, and prognosis. MiR-301a modulates the expression of multiple genes, other noncoding RNAs, and signaling cascade via direct or indirect regulation in human cancer proliferation, migration, invasion, angiogenesis, and radio- or chemotherapy resistance. Cancer cell-associated miR-301a affects the tumor microenvironment through the alteration of immune function and cancer metabolism. These findings highlight the functional roles, clinical implications, and therapeutic relevance of miR-301a in various human cancers.

Gray matter based spatial statistics framework in the 1-month brain: insights into gray matter microstructure in infancy.

The neurodevelopmental epoch from fetal stages to early life embodies a critical window of peak growth and plasticity in which differences believed to be associated with many neurodevelopmental and psychiatric disorders first emerge. Obtaining a detailed understanding of the developmental trajectories of the cortical gray matter microstructure is necessary to characterize differential patterns of neurodevelopment that may subserve future intellectual, behavioral, and psychiatric challenges. The neurite orientation dispersion density imaging (NODDI) Gray-Matter Based Spatial Statistics (GBSS) framework leverages information from the NODDI model to enable sensitive characterization of the gray matter microstructure while limiting partial volume contamination and misregistration errors between images collected in different spaces. However, limited contrast of the underdeveloped brain poses challenges for implementing this framework with infant diffusion MRI (dMRI) data. In this work, we aim to examine the development of cortical microstructure in infants. We utilize the NODDI GBSS framework and propose refinements to the original framework that aim to improve the delineation and characterization of gray matter in the infant brain. Taking this approach, we cross-sectionally investigate age relationships in the developing gray matter microstructural organization in infants within the first month of life and reveal widespread relationships with the gray matter architecture.

Gender Dimensions of Vulnerabilities, Adaptations and Alternative Livelihoods of the Closed Season in Elmina – Ghana: A Qualitative Study

A closed season policy has emerged as an ocean governance strategy aimed at protecting and conserving fish stocks across countries and coastal areas. Its implementation has produced traces of vulnerabilities, and forms of livelihood adaptations and alternative livelihood opportunities. However, little is known about how these occur among gender groups. This paper therefore focuses on the gender dimensions of vulnerabilities, adaptations and alternative livelihoods during the closed season in Elmina, Ghana, within the feminist political ecology framework. It employed Focus Group Discussions (FGDs) from purposively selected fishermen and fish processors. The study found significant differences in the vulnerability patterns among the gender groups, albeit some similarities. We further observed more fluid roles among the women than the men because the women were ready to undertake alternative livelihood options that were traditionally male-based during the closed season. Based on these results, we contend that political decisions toward environmental sustainability may create vulnerability and fluid adaptation patterns which may vary among gender groups in the light of their differential patterns of access, control and positionalities within the fishing industry.

Abstract C097: PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry

Abstract Aggressive prostate cancer (PCa), including castrate-resistant and neuroendocrine subtypes, is projected to increase in incidence 5% each year. Aggressive PCa disproportionally impacts African American men, has limited effective treatment options and high mortality rates. Although racial disparities are established in PCa development, attributed to multiple contributory factors including systemic racism, differences in socioeconomic status and distrust in the medical system, work is still needed to understand the contribution of biological factors. We found the exon 9 region of plasmacytoma variant translocation 1 (PVT1) overexpressed in aggressive PCa cell lines derived from African American (AA) men. We found PVT1 exon 9 overexpression induced phenotypic changes to normal prostate epithelial cells in vitro and led to tumor formation in vivo. RNA-sequencing analysis revealed 156 significantly differentially expressed genes influenced by PVT1 exon 9 overexpression and radical S-adenosyl methionine domain containing 2 (RSAD2) was the top significantly overexpressed gene (log2Fold change 1.71, p-value &amp;lt; 0.05). We utilized the GSE223405 publicly available dataset to identify whether our identified PVT1 exon 9 downstream genes were enriched in AA prostate cancer cells. RSAD2 was significantly overexpressed in AA prostate cancer cells compared to prostate cancer cells from men of European ancestry (moEA) (log2Fold change 6.18, p-value &amp;lt; 0.05). Comparing normal cells to prostate cancer cells between these groups, we found that normal AA prostate cells had significantly higher expression of RSAD2 (log2fold change 4.25, p-value &amp;lt; 0.001) whereas moEA samples did not (log2fold change 0.837, p-value=0.150). From analysis of data obtained from cBioPortal, we found RSAD2 alteration significantly correlates (p-value &amp;lt; 0.001) with self-identified race and copy number overexpression of RSAD2 was found to be enriched in AA patients (18.16% moEA versus 24% AA). Finally, we found 88.6% of the significantly differentially expressed genes within our PVT1 exon 9 RNA-sequencing dataset were significantly differentially expressed in GSE223405 AA samples and of those, 51.7% of genes exhibited a similar differential expression pattern suggesting that the PVT1 exon 9/RSAD2 dependent pathway may be more prominent in AA men. Mechanistically, we found two differing pathways of RSAD2 overexpression in aggressive prostate cancer cell models, one dependent and one independent of PVT1 exon 9 overexpression, with similar but differing biological functions related to epigenetic processes and metabolism. Ongoing work is investigating the RSAD2 and PVT1 exon 9 expression axis in a diverse set of human prostate cancer tissues and investigating their utilization as a therapeutic target in prostate cancer. Citation Format: Rachel E. Sexton-Bonacci1, Murtaza Barkarar1, Chindeum Udekwu1, Olorunseun O. Ogunwobi1. PVT1 exon 9-dependent overexpression of RSAD2 is a characteristic of prostate cancer in males of African ancestry [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C097.

Abstract C087: Distinct gene expression and DNA methylation pattern associated with poor outcome of B-cell acute lymphoblastic leukemia in Hispanic/Latino children

Abstract The risk of developing Acute Lymphoblastic Leukemia (B-ALL) in Hispanic/Latino (HL) children is 1.2-1.75 greater that Non-Hispanic whites (NHW) and after correcting for socioeconomic factors, mortality is 40% higher in HL children. H/L children have a higher incidence of high-risk genetic variations: a 2-fold greater rate of IKZF1 deletion (IKZF1-del) and a 4-fold greater rate of CRLF2 translocations. IKZF1-del is associated with chemotherapy resistance and CRLF2 translocations represent Ph-like status. These two genetic alterations are concomitant in H/L children. 94% of H/L patients with CRLF2 translocation had a coexisting IKZF1-del. Despite evidence of specific genomic alterations in B-ALL in H/L children, potential differences in gene expression in B-ALL from H/L vs. NHW children has not been studied. Here, we used transcriptomic and genomic approach to determine the role of specific mutations and genetic background in regulation of gene expression in B-ALL from H/L and NHW children and to gain insight into molecular mechanisms that regulate cellular proliferation and chemotherapy resistance. RNA-seq was performed on B-ALL from 42 H/L and 18 NHW children and differential gene expression patterns were compared between the two ethnic groups. Gene set enrichment analysis (GSEA), Gene ontology (GO), and Ingenuity pathway analysis (IPA) were performed. In addition, we performed separate analysis and compared both ethnic groups with wild-type status of IKZF1 (IKZF1-WT). We performed DNA methylation signature analysis using reduced representation bisulfite sequencing on 8 H/L and 8 NHW B-ALL samples. Results showed increased expression of the genes that regulate Immune and inflammatory response, interferon signaling, and JAK/STAT pathway in H/L compared to NHW B-ALL cells. These expression changes were more pronounced in IKZF1-del B-All cells. In contrast, H/L B-ALL cells have reduced expression of the genes that regulate genome stability, cell cycle checkpoint signaling, and specific amino acid synthesis pathways. IPA showed upregulated interferon, Tec Kinase, and CDK5 signaling in B-ALL cells of H/L compared to NHW children. Compared. DNA Methylation analysis showed distinct patterns associated with altered expression of several oncogenes in B-ALL from H/L, compared to NHW children. In conclusion, H/L B-ALL has a distinct expression of the genes that regulate signaling pathways that promote cellular proliferation and chemotherapy resistance that are different from B-ALL in NHW children. Results identified therapeutic targets and tumor vulnerabilities that can be used for precision medicine approach to reduce disparities in B-ALL outcome in H/L children. Citation Format: Sinisa Dovat, Joseph Schramm, Daniel Bogush, Dhimant Desai, Bing He, Dhimant Desai, Arati Sharma. Distinct gene expression and DNA methylation pattern associated with poor outcome of B-cell acute lymphoblastic leukemia in Hispanic/Latino children [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C087.

Abstract C103: Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer

Abstract Colorectal cancer (CRC) is the most prevalent gastrointestinal cancer, the third most common malignancy and the second leading cause of cancer-related mortality worldwide. The American Cancer Society (ACS) estimates 152,810 new cases of colorectal cancer, with an estimated 53,010 deaths in 2024. Typically diagnosed in older adults, CRC incidence is rising among younger individuals, particularly in Hispanics (16.5%) compared to non-Hispanic whites (8.7%). Due to the lack of timely screenings in this ethnic group, further research is crucial to identify novel biomarkers and therapeutic targets for improved early detection and intervention. To accomplish this goal, we performed RNA-sequencing of Hispanic and non-Hispanic White (NHW) CRC tissues. The transcriptomic analysis revealed differential gene expression patterns in Hispanic and NHW populations when compared to respective normal adjacent tissues (NATs). We identified 3577 differentially expressed genes (DEGs) in Hispanic CRC samples and 2971 DEGs in NHW CRC samples, of which 1831 DEGs were unique to Hispanic. Based on the preliminary analysis we hypothesized that unique DEGs from the Hispanic population could help identify potential pathways contributing to CRC progression. Among these 1831 unique DEGs, many of the genes are associated with cholesterol and fatty acid synthesis pathway. The cholesterol biosynthesis pathway is a highly diverse and interconnected signaling pathway, playing essential roles in cellular function and systemic homeostasis. Its complexity and regulatory mechanisms make it a critical area of study in cancer. Studies indicate that Hispanics and African Americans with high cholesterol tend to have higher Body mass index (BMI) levels compared to Whites which has an increased risk of colorectal cancer. However, the role of cholesterol metabolism and fatty acid metabolism in CRC have not been studied from the Hispanic health disparities perspective. From the 1831 DEGs, we selected those in the cholesterol and fatty acid synthesis pathways with significant log2 fold changes (≤ -2 or ≥ +2) and adjusted p-values (FDR ≤ 0.05). Our bioinformatics analysis identified four key DEGs: LCN2, DHCR7, PCSK9 and SQLE. The expression levels of these genes were examined in Hispanic CRC vs. NHW CRC tissue samples using qRT-PCR. Elevated expression of LCN2 and SQLE was observed in late-stage Hispanic CRC tissues compared to NHW CRC tissues, while DHCR7 exhibited high expression in early-stage Hispanic CRC. On the other hand, PCSK9 showed low expression in both early and late stages of Hispanic CRC, suggesting potential ethnicity-specific molecular signatures in CRC progression. Moving forward, protein level studies and functional analysis of these DEGs in Hispanic CRC tissues and organoids will enhance our understanding of the role of cholesterol and fatty acid synthesis pathway proteins. Thus, elucidating novel molecular mechanisms underlying CRC progression could lead to identification of potential Hispanic specific biomarkers and therapeutic targets for early diagnosis and intervention. Citation Format: Somrita Roy, Soumya Nair, MD Zahirul Islam Khan, Sourav Roy. Exploring ethnicity-specific molecular mechanism of cholesterol and fatty acid synthesis pathway in Hispanic colorectal cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C103.