Identification of Regulatory Elements in Primary Sensory Neurons Involved in Trauma-Induced Neuropathic Pain.
Chronic pain is a significant public health issue that is often refractory to existing therapies. Here we use a multiomic approach to identify cis-regulatory elements that show differential chromatin accessibility and reveal transcription factor (TF) binding motifs with functional regulation in the rat dorsal root ganglion (DRG), which contain cell bodies of primary sensory neurons, after nerve injury. We integrated RNA-seq to understand how differential chromatin accessibility after nerve injury may influence gene expression. Using TF protein arrays and chromatin immunoprecipitation-qPCR, we confirmed C/EBPγ binding to a differentially accessible sequence and used RNA-seq to identify processes in which C/EBPγ plays an important role. Our findings offer insights into TF motifs that are associated with chronic pain. These data show how interactions between chromatin landscapes and TF expression patterns may work together to determine gene expression programs in rat DRG neurons after nerve injury.
View details for DOI 10.1007/s12035-023-03673-5
View details for PubMedID 37792259
View details for PubMedCentralID 5215096
Two cases of MPXV infection during pregnancy in heterosexual cisgender women without classic cutaneous lesions, Northern California, 2022.
2023; 33: e01881
As part of an epidemiologic survey, we screened remnant samples collected for STI testing for mpox virus. We identified two cases of presumed MPXV infection in pregnant, heterosexual cisgender women. Here, we describe their pregnancy and birth outcomes. Both patients required induction of labor and experienced labor complicated by chorioamnionitis.
View details for DOI 10.1016/j.idcr.2023.e01881
View details for PubMedID 37680215
View details for PubMedCentralID PMC10480306
Prevalence of Mpox (Monkeypox) in patients undergoing STI screening in northern California, April-September 2022.
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
2023; 164: 105493
Despite the sharp increase in mpox (formerly monkeypox) incidence and the wide geographic spread of mpox during the 2022 outbreak, the community prevalence of infection remains poorly characterized. This study is a retrospective epidemiologic survey to estimate mpox prevalence.Samples obtained for sexually transmitted infection (STI) testing from April to September 2022 in the public hospital and clinic system of San Mateo County, California were screened for mpox virus (MPXV) using polymerase chain reaction.16/1,848 samples from 11/1,645 individuals were positive for MPXV by qPCR. 4/11 individuals with positive MPXV testing were cisgender women, 2 of whom were pregnant at the time of sample collection. Both deliveries were complicated by chorioamnionitis. Anorectal and oropharyngeal samples were the most likely to be positive for MPXV (4/60 anorectal samples and 4/66 oropharyngeal samples compared with 5/1,264 urine samples and 3/445 vaginal samples).Our study is one of the first epidemiologic surveys for MPXV infection outside of sexual health/STI clinic settings. Relatively high rates of MPXV from oropharyngeal and anorectal samples reinforces the importance of MPXV testing at various anatomic sites, particularly if patients are presenting with non-lesional symptoms (pharyngitis, proctitis). However, the United States Food and Drug Administration (FDA) has not yet authorized non-lesional MPXV testing. The identification of MPXV in women in our cohort suggests that the rates of mpox in women may have previously been underestimated and highlights the risk of pregnancy complications associated with mpox.
View details for DOI 10.1016/j.jcv.2023.105493
View details for PubMedID 37220710
View details for PubMedCentralID PMC10184869
Retrospective Screening of Clinical Samples for Monkeypox Virus DNA, California, USA, 2022.
Emerging infectious diseases
2023; 29 (4): 848-850
We retrospectively screened oropharyngeal and rectal swab samples originally collected in California, USA, for Chlamydia trachomatis and Neisseria gonorrhoeae testing for the presence of monkeypox virus DNA. Among 206 patients screened, 17 (8%) had samples with detectable viral DNA. Monkeypox virus testing from mucosal sites should be considered for at-risk patients.
View details for DOI 10.3201/eid2904.221576
View details for PubMedID 36918374
View details for PubMedCentralID PMC10045697
CCAAT enhancer binding protein gamma (C/EBP-gamma): An understudied transcription factor.
Advances in biological regulation
2022; 84: 100861
The CCAAT enhancer binding protein (C/EBP) family of transcription factors are important transcriptional mediators of a wide range of physiologic processes. C/EBP-gamma is the shortest C/EBP protein and lacks a canonical activation domain for the recruitment of transcriptional machinery. Despite its ubiquitous expression and ability to dimerize with other C/EBP proteins, C/EBP-gamma has been studied far less than other C/EBP proteins, and, to our knowledge, no review of its functions has been written. This review seeks to integrate the current knowledge about C/EBP-gamma and its physiologic roles, especially in cell proliferation, the integrated stress response, oncogenesis, hematopoietic and nervous system development, and metabolism, as well as to identify areas for future research.
View details for DOI 10.1016/j.jbior.2022.100861
View details for PubMedID 35121409
Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain
JOURNAL OF NEUROINFLAMMATION
2021; 18 (1): 185
Efforts to understand genetic variability involved in an individual's susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms.To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund's adjuvant (CFA) in rats.Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models.Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG.
View details for DOI 10.1186/s12974-021-02228-6
View details for Web of Science ID 000690987200002
View details for PubMedID 34446036
View details for PubMedCentralID PMC8390277