Non-diphtheriae Corynebacterium species have been increasingly recognized as the causative agents of infections in humans. Differential identification of these bacteria in the clinical microbiology laboratory by the most commonly used biochemical tests is challenging, and normally requires additional molecular methods. Herein, we present the annotated draft genome sequences of two isolates of “difficult-to-identify” human-pathogenic corynebacterial species: C. xerosis and C. minutissimum. The genome sequences of ca. 2.7 Mbp, with a mean number of 2,580 protein encoding genes, were also compared with the publicly available genome sequences of strains of C. amycolatum and C. striatum. These results will aid the exploration of novel biochemical reactions to improve existing identification tests as well as the development of more accurate molecular identification methods through detection of species-specific target genes for isolate's identification or drug susceptibility profiling.
Circadian rhythms are mechanisms that measure time on a scale of about 24 h and that adjusts our body to external environmental signals. Core circadian clock genes are defined as genes whose protein products are necessary components for the generation and regulation of circadian rhythms. Circadian proteins also regulate genes involved in either cell division or death; and a perturbation of the balance among these processes leads to cancer development and progression. A key aspect of cancer research is identifying new regulatory pathways involved in proliferation and differentiation of cell. Disruption of circadian rhythm has recently emerged as a new potential risk factor in the development of cancer, pointing to the core gene period 2 (per2) as a tumor suppressor. However, it remains unclear how the circadian network regulates tumor suppression, nor which, if any, of its components is either the ultimate effector that influences the fate of the cell. Initial experiments were devoted to identifying new interacting partners for Per2 using a two-hybrid system. Interestingly, among the positive clones analyzed was the oncogenic protein Mdm2. This result was validated by immunoprecipitation of recombinant and endogenous Per2/Mdm2 complexes from unstressed cells. Pull-down assays using tagged-expressed proteins fragments and labeled proteins were later used to map the interacting regions between Per2 and Mdm2. Our results show Mdm2 binds to the central flexible region of Per2 known to interact with various protein partners. Thus, we hypothesized that binding of Mdm2 to Per2 might act by mediating its ubiquitination and therefore altering Per2 stability. We next examined the formation of the Mdm2/p53/Per2 complex by immunoprecipitation. Our data show anti-p53 antibody is able to co-immunoprecipitate Per2 and Mdm2. Moreover, in vitro and in vivo ubiquitination assays show that binding of Per2 to p53 prevented ubiquitination of p53 by Mdm2 without altering their binding. Immunofluorescence studies using H1299 cells (p53-) confirmed Per2 role in p53 stabilization and for localization. Overall our results suggest that Mdm2 modulates the stability of Per2 and p53 in unstressed cells, and might be responsible for the oscillatory levels of these proteins observed in a 24 h cycle. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-06-05.
The circadian clock is a molecular mechanism that synchronizes environment variations with physiological changes. Disruption of the circadian clock has been linked to increased risk in diseases and a number of disorders (e.g. jet lag, insomnia, coronary heart disease and cancer). Period 2 (PER2), a circadian protein, is at the center of the clock's function. The complete loss of per2 has been shown to be common in several types of cancer including breast and ovarian. Epidemiological studies established a correlation between circadian disruption and the development of estrogen dependent tumors. The expression of estrogen receptor alpha (ERa) mRNA oscillates in a 24-hour period and, unlike PER2, ERa peaks during the light phase of the day. Because up regulation of ER relates to tumor development, defining the mechanisms of ERa expression will contribute to our comprehension of cellular proliferation and regulation of normal developmental processes. The overall goal of this project is to investigate the molecular basis for circadian control of estrogen receptor alpha (ERa) transcription. Transcriptional activation of ERa was measured using a reporter system in Chinese Hamster Ovary and MCF-7 cell lines. Data show that PER2 influence ERa transcription through a non-canonical mechanism independent of its circadian counterparts. Promoter analysis using the Alibaba 2.0 suite revealed the presence of various putative novel partners. Among them, OCT-1 was found to directly interact with Per2, in vitro, and with corresponding response element within the ERa promoter. The predicted binding site of OCT-1 is 267 bps upstream of the promoter. Pull-down assays were used to map direct interaction of various PER2 recombinant proteins and the DNA-binding domain of OCT-1. Radiolabeled OCT-1 was found to bind to the C-terminal end of PER2. Electrophoretic mobility shift assays were used to determine direct binding of OCT-1 to the promoter. ChIP assay confirmed the recruitment of PER2 to the estrogen promoter by OCT-1. Fluorescence anisotropy and surface plasmon resonance were employed to establish the binding affinity of OCT-1 to the ERa promoter and PER2. OCT-1 was found to have a high affinity for the ERa promoter (∼10 nM). Furthermore, OCT-1 recruits PER2 to the estrogen promoter. Preliminary data suggests that the transcription factor PER2 might play a role in the regulation of the estrogen promoter. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-03-04.
Treacher Collins syndrome is a genetic disorder resulting in congenital craniofacial malformation. Patients typically present with downslanting palpebral fissures, lower eyelid colobomas, microtia, and malar and mandibular hypoplasia. This autosomal dominant disorder has a variable degree of phenotypic expression, and patients have no associated developmental delay or neurologic disease. Care for these patients requires a multidisciplinary team from birth through adulthood. Proper planning, counseling and surgical techniques are essential for optimizing patient outcomes. Here the authors review the features, genetics, and treatment of Treacher Collins syndrome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.