Functional elements demarcated by histone modifications in breast cancer cells

AbstractHistone modifications are regarded as one of markers to identify regulatory elements which are DNA segments modulating gene transcription. Aberrant changes of histone modification levels are frequently observed in cancer. We have employed ChIP-Seq to identify regulatory elements in human breast cancer cell line, MCF-7 by comparing histone modification patterns of H3K4me1, H3K4me3, and H3K9/14ac to those in normal mammary epithelial cell line, MCF-10A. The genome-wide analysis shows that H3K4me3 and H3K9/14ac are highly enriched at promoter regions and H3K4me1 has a relatively broad distribution over proximity of TSSs as well as other genomic regions. We identified that many differentially expressed genes in MCF-7 have divergent histone modification patterns. To understand the functional roles of distinctively histone-modified regions, we selected 35 genomic regions marked by at least one histone modification and located from 3 to 10kb upstream of TSS in both MCF-7 and MCF-10A and assessed their transcriptional activities. About 66% and 60% of selected regions in MCF-7 and MCF-10A, respectively, enhanced the transcriptional activity. Interestingly, most regions marked by H3K4me1 exhibited an enhancer activity. Regions with two or more kinds of histone modifications did show varying activities. In conclusion, our data reflects that comprehensive analysis of histone modification profiles under cell type-specific chromatin environment should provide a better chance for defining functional regulatory elements in the genome

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

111Ysciescopu

Pyramid Inter-Attention for High Dynamic Range Imaging

This paper proposes a novel approach to high-dynamic-range (HDR) imaging of dynamic scenes to eliminate ghosting artifacts in HDR images when in the presence of severe misalignment (large object or camera motion) in input low-dynamic-range (LDR) images. Recent non-flow-based methods suffer from ghosting artifacts in the presence of large object motion. Flow-based methods face the same issue since their optical flow algorithms yield huge alignment errors. To eliminate ghosting artifacts, we propose a simple yet effective alignment network for solving the misalignment. The proposed pyramid inter-attention module (PIAM) performs alignment of LDR features by leveraging inter-attention maps. Additionally, to boost the representation of aligned features in the merging process, we propose a dual excitation block (DEB) that recalibrates each feature both spatially and channel-wise. Exhaustive experimental results demonstrate the effectiveness of the proposed PIAM and DEB, achieving state-of-the-art performance in terms of producing ghost-free HDR images

Outbreak of carbapenem-resistant Enterobacterales at a long-term care facility in Seoul, Korea: surveillance and intervention mitigation strategies

OBJECTIVES Because effective decolonization options are not available, and treatment options are limited, carbapenem-resistant Enterobacterales (CRE) constitute increasingly threatening nosocomial pathogens. To prevent CRE-associated transmission and ensure patient safety, healthcare personnel and everyone in contact with CRE-infected patients must implement stringent infection control practices. This report describes a CRE outbreak, possibly related to a caregiver at a long-term care facility (LTCF), and presents a new surveillance model to improve the infection control of CRE in Seoul, Korea. METHODS The Seoul Metropolitan Government surveillance system identified an outbreak of CRE in an LTCF in 2022. We obtained data on the demographic characteristics and contact histories of the inpatients, medical staff, and caregivers. To isolate the inpatients and employees exposed to CRE, we used rectal swab samples and environmental sampling during the study period (May-December 2022). RESULTS We identified 18 cluster cases (1 caregiver and 17 inpatients) and 12 sporadic cases with CRE, and conducted a complete 197-day follow-up of all cases in the LTCF’s isolation wards. CONCLUSIONS This investigation demonstrated that our surveillance model and targeted intervention, based on the cooperation of the municipal government, public health center, and infection control advisory committee, effectively contained the epidemic at the LTCF. Measures to improve the compliance of all employees in LTCFs with infection control guidelines should also be adopted

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

<div><p>Background</p><p>The generation of induced pluripotent stem cell (iPSC), a substitute for embryonic stem cell (ESC), requires the proper orchestration of a transcription program at the chromatin level. Our recent approach for the induction of pluripotent stem cells from fibroblasts using protein extracts from mouse ESCs could overcome the potential tumorigenicity risks associated with random retroviral integration. Here, we examine the epigenetic modifications and the transcriptome of two types of iPSC and of partially reprogrammed iPSCs (iPSCp) generated independently from adult cardiac and skin fibroblasts to assess any perturbations of the transcription program during reprogramming.</p><p>Results</p><p>The comparative dissection of the transcription profiles and histone modification patterns at lysines 4 and 27 of histone H3 of the iPSC, iPSCp, ESC, and somatic cells revealed that the iPSC was almost completely comparable to the ESC, regardless of their origins, whereas the genes of the iPSCp were dysregulated to a larger extent. Regardless of the origins of the somatic cells, the fibroblasts induced using the ESC protein extracts appear to be completely reprogrammed into pluripotent cells, although they show unshared marginal differences in their gene expression programs, which may not affect the maintenance of stemness. A comparative investigation of the iPSCp generated by unwanted reprogramming showed that the two groups of genes on the pathway from somatic cells to iPSC might function as sequential reprogramming-competent early and late responders to the induction stimulus. Moreover, some of the divergent genes expressed only in the iPSCp were associated with many tumor-related pathways.</p><p>Conclusions</p><p>Faithful transcriptional reprogramming should follow epigenetic alterations to generate induced pluripotent stem cells from somatic cells. This genome-wide comparison enabled us to define the early and late responder genes during the cell reprogramming process to iPSC. Our results indicate that the cellular responsiveness to external stimuli should be pre-determined and sequentially orchestrated through the tight modulation of the chromatin environment during cell reprogramming to prevent unexpected reprogramming.</p></div

Emerging role of vascular burden in AT(N) classification in individuals with Alzheimers and concomitant cerebrovascular burdens.

OBJECTIVES: Alzheimers disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimers pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p&lt;0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimers pathological changes (A-T+, A-N+; p=0.002) and Alzheimers pathological changes (p&lt;0.001) categories. CONCLUSION: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system

Global histone modification signatures of pluripotent and somatic cells.

<p>(A) Experimental overview of the genome-wide analysis of the histone modifications of mESC, iPSCs and the original somatic cells using ChIP-Seq and their gene expression measured via microarray and RNA-seq. (B) The histone modification profiles of the Hox D cluster genes are shown using the UCSC genome browser. The genomic position of the region is indicated on top of the map. (C) Chromosome-wide H3K4me3 peak patterns are compared in different cells. The Hilbert plots of H3K4me3 enrichments at chromosome 1 are visualized using the HilberVis program. (D) The comparison of histone modification patterns between different mESCs and iPSCs. The heatmap represents the distributions of the histone modification near the TSS of 22,086 RefSeq genes. The rows in the all data sets are sorted using the tag density of the mESCs from the highest to the lowest. The position of the TSS and the direction of transcription are denoted using an arrow. The numbers inside the heatmap indicate the Pearson correlation coefficients compared with the mESCs.</p

Identification of early and late responder genes from the partial iPSC analysis.

<p>(A) Categorization of the differentially expressed genes among iPSCps, mESCs, and sFB-G into three groups: the divergent, the convergent, and the resistant genes. (B) The H3K4me3 and H3K27me3 levels were plotted, depending on the responsiveness of the genes to the induction of pluripotency (C) The UCSC genome browser shows the chromatin states of the divergent (Fgf5), convergent (Cdc20), and resistant (Col1a1) genes in all cell types. The positions and directions of transcription of the genes are indicated below the panel. (D) The three groups are listed according to their expression and histone modification fold change values. The gene ontology analysis shows highly significant biological functions associated with the differentially expressed genes. (E) A model for the step-wise acquisition of pluripotency. Sox2 was identified as an early responder gene.</p

Comparative analysis of the protein-based iPSCs and other pluripotent cells.

<p>(A) Hierarchical clustering of the gene expression microarray data for the mESCs (open circles), iPSCs (filled circles), and fibroblasts (filled squares) from different laboratories. The data sets of the mESCs and iPSCs obtained from the same laboratory are marked using grey boxes. The iPSC induction methods are labelled for each iPSC data set: ¹GSE13770, ²GSE24930, ³GSE17004, ⁴GSE27814, ⁵GSE22908, ⁶GSE24046, and ⁷GSE27087. (B-C) The Venn diagram shows the overlap of the differentially expressed genes between mESCs and iPSCs. For comparison, two iPSC* (GSE24046) and iPSC^§ (GSE27814) data sets are also incorporated. (D) The gene expression levels and histone modifications of the differentially expressed genes defined in (B-C) are shown and the Pearson correlation coefficients are presented on the right side of each heatmap.</p