Bacillus Cereus Catheter Related Bloodstream Infection in a Patient with Acute Lymphoblastic Leukemia

Bacillus cereus infection is rarely associated with actual infection and for this reason single positive blood culture is usually regarded as contamination . However it may cause a number of infections, such catheter-related bloodstream infections. Significant catheter-related bloodstream infections (CRBSI) caused by Bacillus spp. are mainly due to B. cereus and have been predominantly reported in immunocompromised hosts. Catheter removal is generally advised for management of infection. In this report, catheter-related bacteremia caused by B. cereus in a patient with acute lymphoblast c leukemia (ALL) in Istanbul Medical Faculty was presented

LncRNA RP11-19E11 is an E2F1 target required for proliferation and survival of basal breast cancer

Long non-coding RNAs (lncRNAs) play key roles in the regulation of breast cancer initiation and progression. LncRNAs are differentially expressed in breast cancer subtypes. Basal-like breast cancers are generally poorly differentiated tumors, are enriched in embryonic stem cell signatures, lack expression of estrogen receptor, progesterone receptor, and HER2 (triple-negative breast cancer), and show activation of proliferation-associated factors. We hypothesized that lncRNAs are key regulators of basal breast cancers. Using The Cancer Genome Atlas, we identified lncRNAs that are overexpressed in basal tumors compared to other breast cancer subtypes and expressed in at least 10% of patients. Remarkably, we identified lncRNAs whose expression correlated with patient prognosis. We then evaluated the function of a subset of lncRNA candidates in the oncogenic process in vitro. Here, we report the identification and characterization of the chromatin-associated lncRNA, RP11-19E11.1, which is upregulated in 40% of basal primary breast cancers. Gene set enrichment analysis in primary tumors and in cell lines uncovered a correlation between RP11-19E11.1 expression level and the E2F oncogenic pathway. We show that this lncRNA is chromatin-associated and an E2F1 target, and its expression is necessary for cancer cell proliferation and survival. Finally, we used lncRNA expression levels as a tool for drug discovery in vitro, identifying protein kinase C (PKC) as a potential therapeutic target for a subset of basal-like breast cancers. Our findings suggest that lncRNA overexpression is clinically relevant. Understanding deregulated lncRNA expression in basal-like breast cancer may lead to potential prognostic and therapeutic applications

Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes

The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity

EWS-FLI1 Utilizes Divergent Chromatin Remodeling Mechanisms to Directly Activate or Repress Enhancer Elements in Ewing Sarcoma

SummaryThe aberrant transcription factor EWS-FLI1 drives Ewing sarcoma, but its molecular function is not completely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repeat elements, which lack evolutionary conservation and regulatory potential in other cell types, EWS-FLI1 multimers induce chromatin opening and create de novo enhancers that physically interact with target promoters. Conversely, EWS-FLI1 inactivates conserved enhancers containing canonical ETS motifs by displacing wild-type ETS transcription factors. These divergent chromatin-remodeling patterns repress tumor suppressors and mesenchymal lineage regulators while activating oncogenes and potential therapeutic targets, such as the kinase VRK1. Our findings demonstrate how EWS-FLI1 establishes an oncogenic regulatory program governing both tumor survival and differentiation

The Relationship between Dioxin-Like Polychlorobiphenyls and IGF-I Serum Levels in Healthy Adults: Evidence from a Cross-Sectional Study

OBJECTIVE: Insulin-like growth factor I (IGF-I) and dioxin-like polychlorobiphenyls (DL-PCBs) have been associated with the pathogenesis of several diseases like cancer, diabetes and growth disorders. Because it has been suggested that organohalogenated contaminants could influence IGF-I levels in adults, the potential relationship between DL-PCBs and IGF-I serum levels was studied in 456 healthy adults from a representative sample of the general population of the Canary Islands (Spain). DESIGN: Free circulating serum levels of IGF-I and IGFBP-3 were measured through an ELISA methodology, while the serum levels of the 12 DL-PCBs congeners (IUPAC numbers # 77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169, and 189) were measured by gas chromatography/mass spectrometry (GC-MS). RESULTS: DL-PCBs 156 and 167, Total DL-PCBs body burden (∑PCBs: sum over the 12 measured DL-PCBs), and Total toxic burden (in terms of toxic equivalence to dioxins: ∑TEQs) showed a trend of inverse association with IGF-I serum levels in the whole studied population. After adjusting for potential confounders, including gender, body mass index (BMI), age, and IGF-binding protein-3 (IGFBP-3), younger (18-45 years) women with lower BMI (<27 kg/m(2)) and detectable levels of DL-PCB-156 showed significantly lower IGF-I levels than those in the same age and BMI subgroup with non-detectable levels of DL-PCB-156 (p<0.001). Similarly, ∑PCBs and ∑TEQs showed a tendency to an inverse association with IGF-I levels in the same group of women (p=0.017 and p=0.019 respectively). CONCLUSIONS: These findings suggest that DL-PCBs could be involved in the regulation of the IGF-system in a way possibly influenced by gender, age and BMI. Although these results should be interpreted with caution, such circumstances could contribute to explain the development of diseases associated to the IGF system