Publications by authors named "Dereje Jima"

Triphenyl phosphate (TPhP) is a widely used organophosphate flame retardant and plasticizer, raising concerns over its health impacts. This study examined the effects of embryonic TPhP exposure on axial skeletal development and metabolism in medaka (), a vertebrate fish model relevant to human bone biology. Medaka embryos were exposed to 1 µM TPhP and assessed through early larval stages.

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Polybrominated diphenyl ethers (PBDEs) are synthetic flame retardants once widely used in furniture, electronics, and other consumer products. Although phased out in the early 2000s, their chemical persistence, recycling into new materials, and leaching from waste sites have led to ongoing environmental contamination and widespread human exposure, especially through diet and indoor dust. This is particularly concerning for developing individuals, who not only accumulate the highest levels via placental transfer, breastfeeding, and behavioral factors, but are also especially vulnerable to long-term effects.

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Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery.

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Background: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear.

Objective: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e.

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Micro- and nanoplastics (MNPs) are widespread environmental pollutants that pose significant health risks. They originate from industrial processes, consumer products, and environmental degradation, inducing oxidative stress through cellular dysfunctions such as membrane interaction, internalization, mitochondrial damage, inflammation, metal ion leaching, and impaired antioxidant defense. Despite increasing evidence of their toxicity-particularly developmental neurotoxicity (DNT) and mitochondrial impairment-our understanding remains limited due to the high costs of animal studies, which reduce the overall size of experimental data.

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  • Microenvironmental factors play a key yet unclear role in the progression of soft tissue sarcomas, especially during their onset.
  • A novel zebrafish model was developed to differentiate among microenvironmental, precancerous, and cancer cells, focusing on malignant peripheral nerve sheath tumors (MPNST), which grow aggressively.
  • The study reveals that specific inflammatory signaling pathways are activated during the transition from precancerous to cancerous states, highlighting the role of macrophages and identifying periostin as a significant protein in MPNST progression.
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Understanding the molecular mechanisms of complex traits is essential for developing targeted interventions. We analyzed liver expression quantitative-trait locus (eQTL) meta-analysis data on 1,183 participants to identify conditionally distinct signals. We found 9,013 eQTL signals for 6,564 genes; 23% of eGenes had two signals, and 6% had three or more signals.

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Squamous cell carcinomas (SCCs), including lung, head & neck, bladder, and skin SCCs often display constitutive activation of the KEAP1-NRF2 pathway. Constitutive activation is achieved through multiple mechanisms, including activating mutations in NFE2L2 (NRF2). To determine the functional consequences of Nrf2 activation on skin SCC development, we assessed the effects of mutant Nrf2 expression, one of the most common activating mutations in human SCCs, on tumor promotion and progression in the mouse skin multistage carcinogenesis model using a DMBA-initiation/TPA-promotion protocol where the Hras A->T mutation (Q61L) is the canonical driver mutation.

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  • Alzheimer's disease is more prevalent in non-Hispanic Blacks compared to non-Hispanic Whites, prompting a study on the role of methylation in this disparity.
  • Researchers analyzed brain tissue DNA to identify differentially methylated regions (DMRs) related to imprint control regions (ICRs) in both AD patients and controls, revealing significant differences in methylation patterns.
  • The study found 81 DMRs in non-Hispanic Black AD patients and 27 in non-Hispanic White AD patients, suggesting that changes in DNA methylation related to genomic imprinting may influence the risk of Alzheimer's and vary between these populations.
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  • Malrotation of the intestine is a common birth defect, and research indicates that exposure to the herbicide atrazine during late-stage development in Xenopus embryos significantly increases the occurrence of this defect.
  • Atrazine disrupts key processes needed for gut tube growth, such as cell arrangement and proliferation, leading to insufficient gut lengthening and altered rotation direction.
  • The study highlights the connection between metabolic disruptions caused by atrazine exposure (such as reduced important metabolites and increased oxidative stress) and intestinal malrotation, suggesting that these metabolic issues play a role in this developmental anomaly.
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  • Differentially methylated imprint control regions (ICRs) play a crucial role in regulating gene expression, and their dysregulation can lead to chronic diseases, but current methods for profiling them are limited.
  • A custom methylation array with 22,819 probes was developed to better assess ICRs, showing promise in comparison to traditional methods like WGBS and the Human Imprintome array.
  • This new tool aims to enhance the accuracy of ICR assessments and facilitate research on their links to diseases and genetic imprinting throughout an individual’s life.
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  • * A meta-analysis of 37 studies revealed that higher MEA is linked to different DNA methylation patterns in offspring at birth, childhood, and adolescence, with significant findings at 473 specific sites associated with maternal factors like smoking and nutrition.
  • * The research underscores the connection between socio-economic status and biological processes, enhancing our understanding of how maternal education impacts health through genetic mechanisms and emphasizing the role of social determinants in health disparities.
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  • Childhood appetitive traits are influenced by early-life epigenetic processes, particularly through DNA methylation (DNAm), where methyl groups attach to DNA and potentially affect appetite regulation.
  • The study analyzed DNAm in cord blood from two cohorts, using multiple regression models to examine how different DNAm patterns correlated with children's eating behaviors reported by parents.
  • While no direct associations were found at individual DNA sites, examining grouped methylation patterns revealed significant connections between DNAm and various appetitive traits, suggesting that DNA methylation in newborns might play a role in shaping eating behaviors as children grow.
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Background: Tobacco smoking during pregnancy is associated with metabolic dysfunction in children, but mechanistic insights remain limited. Hypomethylation of cg05575921 in the aryl hydrocarbon receptor repressor (AHRR) gene is associated with in utero tobacco smoke exposure. In this study, we evaluated whether AHRR hypomethylation mediates the association between maternal smoking and metabolic dysfunction in children.

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  • Seasonal variations at birth can influence DNA methylation, which may affect health outcomes over a person’s lifetime.
  • A study involving multiple cohorts discovered specific DNA methylation patterns linked to different birth seasons, revealing 26 differentially methylated regions (DMRs) at birth and 32 in childhood.
  • Results suggested that geographic latitude plays a role in these associations, linking certain genes to conditions like schizophrenia and asthma, particularly in infants born in higher latitudes (≥50°N).
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  • Childhood appetitive traits, which are linked to obesity risk, are influenced by both genetic and environmental factors, but their exact causes are not well understood.
  • The study meta-analyzed data from two cohorts to explore the relationship between DNA methylation (DNAm) in newborns and early childhood appetitive traits.
  • While no associations were found at the individual DNAm site level, significant correlations were established at the regional level, suggesting that early epigenetic processes may contribute to the development of children's appetitive behaviors.
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Toxicogenomics is a critical area of inquiry for hazard identification and to identify both mechanisms of action and potential markers of exposure to toxic compounds. However, data generated by these experiments are highly dimensional and present challenges to standard statistical approaches, requiring strict correction for multiple comparisons. This stringency often fails to detect meaningful changes to low expression genes and/or eliminate genes with small but consistent changes particularly in tissues where slight changes in expression can have important functional differences, such as brain.

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  • Cadmium (Cd) is a toxic heavy metal linked to severe fetal health issues, including growth restriction and malformations, with unclear mechanisms behind these effects.
  • Researchers used a mouse model to investigate how Cd impacts gene expression in the placenta, revealing a significant increase in a specific long non-coding RNA after Cd exposure.
  • The study suggests that this lncRNA may influence gene expression related to oxidative stress responses, highlighting a potential pathway through which Cd causes negative outcomes in fetal development.
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  • The skin serves as a crucial defense against infections, with keratinocytes activating the type I interferon (IFN) response to combat pathogens.
  • A study involving the deletion of the C/EBPβ transcription factor in mouse epidermis showed increased levels of IFNβ and other interferon-stimulated genes (ISGs) in keratinocytes.
  • The absence of C/EBPβ enhanced the keratinocytes' response to viral and pathogen mimics, leading to greater activation of immune responses and increased cell death through apoptosis, highlighting C/EBPβ's role as a repressor in this protective mechanism.
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Calcium (Ca) is one of the essential mineral nutrients for plant growth and development. However, the effects of long-term Ca deficiency in orphan crops such as Tef [(Eragrostis tef) (Zucc.) Trotter], which accumulate high levels of Ca in the grains, remained unknown.

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Differentiation of multipotent mesenchymal stem cells (MSCs) into bone-forming osteoblasts requires strict coordination of transcriptional pathways. Aryl hydrocarbon receptor ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been shown to alter osteoblast differentiation in vitro and bone formation in multiple developmental in vivo models. The goal of the present study was to establish a global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD exposure.

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  • Ecologists have noted a decline in freshwater biodiversity due to increased salinization, particularly affecting organisms like mayflies, but the physiological impacts of salinity changes on these species remain largely unexplored.
  • The study focuses on N. triangulifer mayflies to investigate how chronic exposure to different salinity levels affects protein expression in the gills, using shotgun proteomics to identify key proteins involved in ion transport.
  • Findings reveal significant changes in protein expression linked to salinity exposure, identifying 710 unique peptide sequences and highlighting critical transporters, while also addressing broader physiological functions related to ATP synthesis and stress response.
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  • Cadmium exposure in adulthood is linked to nonalcoholic fatty liver disease (NAFLD), and rising NAFLD cases in children indicate the importance of early life environmental factors.
  • Research suggests that imprinted genes, especially Zac1, may connect early exposure to disease susceptibility later in life.
  • Experiments in mice revealed that developmental cadmium chloride exposure led to NAFLD characteristics and showed that Zac1 is a significant factor in this programming process, influencing lipid accumulation through its interaction with the Pparγ promoter.
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  • This study analyzed RNA-Seq data from 192 genotyped liver samples, combining it with existing data to create a comprehensive resource for liver gene expression research.
  • The research found strong associations between genetic variations and genes related to drug response, highlighting the necessity of using multiple datasets for accurate results.
  • Additionally, the study developed a novel meta-analysis tool to enhance genetic association studies, showcasing its use in re-analyzing data on neutropenia in pancreatic cancer patients, with all findings accessible through a searchable genome browser.
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  • HIF-PHIs are being developed to treat anemia in CKD, but it's crucial to ensure they are safe for the heart.
  • Genetic variants can potentially predict the risk of adverse cardiovascular effects from these treatments.
  • A specific genetic variant related to EPO levels was identified and tested, showing no increased risk of coronary artery disease, heart attack, or stroke with higher EPO levels, indicating a safer profile for these therapies.
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