Project description:Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is a ubiquitous environmental pollutant and may act as an endocrine disruptor. Early life exposures to DEHP may result in anti-androgenic effects, impairing the development of the male reproductive tract. However, data on the long-lasting consequences of such DEHP exposures on adult male reproductive function are still rare and discrepant. Previously, we identified two novel plasticizers, 1,4 butanediol dibenzoate (BDB) and dioctyl succinate (DOS), as potential substitutes for DEHP that did not reproduce classically described endocrine disrupting phenotypes in prepubertal male offspring after maternal exposure. Here, we investigated the consequences of in utero and lactational exposure to BDB and DOS on adult male rat reproductive function in a comparative study with DEHP and a commercially available alternative plasticizer, 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH). Timed pregnant Sprague-Dawley rats were gavaged with vehicle or a test chemical (30 or 300 mg/kg/day) from gestation day 8 to postnatal day 21. While DEHP exposure (300 mg/kg/day) significantly increased epididymal weight in the adult, exposure to DINCH, BDB or DOS did not affect reproductive organ weights, steroid levels or sperm quality. Using a toxicogenomic microarray approach, we found that adult testicular gene expression was affected by exposure to the higher dose of DEHP; transcripts such as Nr5a2, Ltf or Runx2 were significantly downregulated, suggesting that DEHP was targeting estrogen signaling. Lesser effects were observed after treatment with either DINCH or BDB. DOS exposure did not produce such effects, confirming its potential as a responsible substitute for DEHP. The data deposited correspond to testicular gene expression in 90 day-old Sprague-Dawley rats after exposure to CORN OIL and 30 or 300 mg/kg/day DEHP, DINCH, BDB or DOS from gestational day 8 to post-natal day 21
Project description:Phthalate plasticizers are being phased out of consumer products because of their endocrine disrupting properties. This has resulted in a need to find safe alternatives that can plasticize polyvinyl chloride (PVC) while being inexpensive and biodegradable. We aim to study the toxicogenomic profile of mono-(2-ethylhexyl) phthalate (MEHP, the active metabolite of bis(2-ethylhexyl) phthalate, DEHP), the commercial plasticizer 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH), and three plasticizers in development (1,4 butanediol dibenzoate (BDB), dioctyl succinate (DOS), and dioctyl maleate (DOM)) using the immortalized TM4 Sertoli cell line. Each sample contains four biological replicates except for DOS that contains three. The control is 1.0% DMSO as this was the vehicle used to solubilize the test compounds.
Project description:Transcriptional profiling of RNA samples from un-infected Rhesus Bone Marrow Derived Macrophages (RhBMDMs) exposed to IMDM complete media used as control were compared to RNA from RhBMDMs infected for 24 hr with 'dos' mutants of Mtb viz. MtbΔdosR, MtbΔdosS, or MtbΔdosT
Project description:Herein, we set out to investigate the responses to first-line therapies (DOS, XELOX, and anti-HER2-based therapies) for GC through a comprehensive proteomic analysis. We constructed a GC cohort that covered three clinical therapy subcohorts, including a DOS subcohort (44 patients treated with DOS therapy), an XELOX subcohort (70 patients treated with XELOX therapy) and a HER2 subcohort (71 patients who received anti-HER2-based therapy).
Project description:Trichomes contribute to plant tolerance of abiotic stresses, such as heat, and biotic stresses, including insect herbivory. Leaves of Brassica napus are typically glabrous or near-glabrous; however, a small number of hirsute accessions were identified in international germplasm collections that produced up to 300 trichomes on the earliest leaves. To investigate the genetic basis of this trait, trichome density on the abaxial and adaxial leaf surfaces, leaf margins, and petioles of the 3rd and 6th leaves was assessed in a doubled haploid (DH) population derived from a cross between a glabrous line (NAM-0) and a hirsute line (DOS-2). Lines were genotyped using a Brassica 60K SNP BeadChip array. A major quantitative trait locus (QTL) controlling trichome density was identified on chromosome C01 that overlapped with regions previously mapped in the C-genome species B. oleracea and B. villosa. In B. napus, this QTL spanned 5.65 Mb and with a 1.7 Mb deletion in the hirsute DOS-2 parent. A gene encoding a novel, R3 single-repeat, MYB protein related to the trichome repressor TRIPTYCHON was identified within the shared region and designated TRIPTYCHON-LIKE (TRL). DOS-2 harbors a single BnTRL gene, whereas NAM-0 contains four tandemly-linked copies, although BnTRL transcript abundance did not correlate directly with trichome density. The expanded TRL gene family is unique to the Brassicaceae and BnTRL proteins physically interact with the GL1-binding domain of GL3, a core component of the GL1–GL3–TTG1 trichome initiation complex. Analysis of additional genes within the shared QTL region or absent in DOS-2 revealed regulators associated with chromatin modification (e.g. ADA2b, RBBP6-like), hormone signaling (ARR2, GH3, JAM3, HAT4), cytoskeletal dynamics (SPIRAL2, MAP65-2, MAP70-5, SPIKE1), and cell growth (SVH3, LIP5). Hormone application experiments demonstrated genotype- and tissue-specific responses on trichome production, particularly to jasmonate and gibberellin. Together, these results indicate that the CO1 locus controlling trichome abundance in B. napus is complicated and may affect regulation of chromatin state, hormonal pathways, cytoskeletal organization, and cell growth, in addition to the assembly of the trichome regulatory complex.
Project description:Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.