Disappearance of Temporal Collinearity in Vertebrates and Its Eventual Reappearance

In 1999 T. Kondo and D. Duboule performed excisions of posterior upstream DNA domains in mouse embryos and they observed that for an extended excision (including Evx gene) the Hox genes of the cluster were simultaneously expressed with the first Hoxd1 gene ‘as if’ Temporal Collinearity (TC) had disappeared. According to a Biophysical Model (BM) during Hox gene expression, Hox clusters behave similar toexpanding elastic springs. For the extended upstream DNA excision, BM predicts the TC disappearance and an experiment is proposed to test this BM prediction. In the chick limb bud C. Tickle et al. observed that the excision of the apical ectodermal ridge (AER) caused the inhibition of HoxA13 expression. However, the implantation of FGF soaked beads at the tip of the limb could surprisingly rescue HoxA13 expression after 24 hours so that TC is restored.Brachyury transcription factor (TF) is essential in identifying the targets of this transcription and a chromatin immunoprecipitation microarray chip (ChIP-chip) was produced which can be inserted in the mouse embryonic cells. It is here proposed to insert this chip in the mutant cells where TC has disappeared and compare it to the limb bud case.Is TC restored? It is an important issue worth exploring.

Transcriptional control of hypoxic hyphal growth in the fungal pathogen Candida albicans

Background: The ability of Candida albicans, an important human fungal pathogen, to develop filamentous forms is a crucial determinant for host invasion and virulence. Filamentation is triggered by different host environmental cues such as temperature and pH. Hypoxia, the dominant conditions that C. albicans encounters inside the human host, promote filamentation, however, the contributing mechanisms remain poorly characterized. Methods: We performed a quantitative analysis of gene deletion mutants from different collections of protein kinases and transcriptional regulators in C. albicans to identify specific modulators of the hypoxic filamentation. We used genome-wide transcriptional profiling (Microarrays) and promoter occupancy (ChIP-chip) to characterize regulons of two transcription factors that were associated with the hypoxic filamentation. Genetic interactions were also used to assess functional relationships among the newly identified modulators of hypoxic filamentation and the well-known C. albicans core morphogenetic regulators. Results: Our genetic screen uncovered two transcription factors, Ahr1 and Tye7, that act as prominent regulators of C. albicans filamentation specifically under hypoxia. Both ahr1 and tye7 mutants exhibited a hyperfilamentous phenotype specifically under an oxygen-depleted environment suggesting that these transcription factors act as a negative regulator of hypoxic filamentation. By combining microarray and ChIP-chip data, we have characterized the set of genes that are directly modulated by Ahr1 and Tye7. We found that both Ahr1 and Tye7 modulate a different set of genes and biological processes. Our genetic epistasis analysis supports our genomic finding and suggests that Ahr1 and Tye7 act independently to modulate hyphal growth in response to hypoxia. Furthermore, our genetic interaction experiments uncovered that Ahr1 and Tye7 repress the hypoxic filamentation growth via the Efg1 and Ras1/Cyr1 pathways, respectively. Conclusion: In sum, this investigation represents an informative resource toward the understanding of how hypoxia, the predominant condition inside the host, shapes the invasive filamentous growth of C. albicans.

Supporting Children and Families During the Kindergarten Transition

This chapter describes the theoretical basis for and implementation of a kindergarten-transition-focused home visiting program, the connection-focused home-visiting intervention program (CHIP). CHIP was designed to support children and their families during the kindergarten transition through development of strong connections between parents, children, teachers, schools, and communities. In this chapter, the authors explain the theoretical framework that guided the development of CHIP and key features of the program design, including connection development, the use of transition coordinators, and individualization. In addition, this chapter includes descriptions of scenarios encountered during CHIP that exemplify the nature of the program and design decisions. Finally, this chapter provides a summary of early evidence of program effectiveness and directions for continued research.

A Unique Histone H3K4me3 Genome Binding Pattern Identified in a Cancer Pedigree with anMLL3Germline Mutation

Background and Objective: Evidence suggests that alterations in histone modifications are crucial in cancer development and progression. Among these, histone 3 lysine 4 trimethylation (H3K4me3) which is one of the most common histone modifications, is found in promoters of active genes and is proposed to promote gene expression. Aberrant H3K4 methylation is association with cancer. In our previous study, we found a germline MLL3 stop codon mutation in a Chinese pedigree. MLL3 proteins act as methyltransferase and regulate H3K4 methylation. Our study aims to evaluate the H3K4me3 genome binding pattern in this cancer pedigree with MLL3 mutation and have further understanding about pathogenesis in this pedigree. Also we hope to find valuable epigenetic marker of cancer. Materials and Methods: To evaluate 3 cancer patients in a Chinese pedigree with a heterozygous stop codon mutation in MLL3 (coding a histone H3K4me3 methyltransferase) segregating with colorectal carcinoma (CRC) and acute myeloid leukemia (AML) and a mutation-free normal control, ChIP-chip analyses were performed to determine which promoters coprecipitated with the H3K4me3 antibody in both patients and control. The pulled-down genes were mapped to Kyoto Encyclopedia Of Genes And Genomes (KEGG) pathways. Results:We selected 1 AML patient, 2 CRC patients, and 1 normal control from a Chinese pedigree. A previous study showed that the 3 patients all harbored an MLL3 stop codon mutation. MLL3 belongs to the human TRX/MLL family and is an important mammalian H3K4 methyltransferase. In this study, using ChIP-chip, we detected the global promoter occupancy profile of H3K4me3 in the two different tumor types compared with a normal control. Compared with the normal control, H3K4me3 differentially bound to the promoter regions of 2425 (CRC), 22319 (CRC), and 2385 (AML) genes in the three patients, with an overlap of 877 genes between AML and CRC tumors. To our surprise, the total numbers of promoters pulled down by the H3K4me3 antibody were not significantly different between the 3 cancer patients and the mutation-free normal control. However, the H3K4me3 binding patterns were unique in the cancer patients compared with the normal control. We also noticed a subtle difference in H3K4me3 binding patterns between the AML patient and the 2 CRC patients. The mother-son pair (CRC-AML) and the sister pair (CRCs) each should have 50% genetic similarities (sex chromosome genes were excluded); however, given the same MLL3 nonsense mutation, the CRC mother-AML son pair showed greater differences in H3K4me3 pulled-down genes than did the CRC sister pair. To understand the possible biological effects of H3K4me3 in AML and CRC, we annotated the functions of the identified genes by mapping them to KEGG pathways. Although the number of identified genes was not significantly differ between patients and control, we found an unique profile of H3K4me3 in AML and CRC patients compared with control that the identified genes were concentrated in the carcinogenesis-associated pathways, including the TGF-beta, Wnt, and MAPK signaling pathways. Conclusions:The results indicate that the H3K4me3 patterns are differentially altered in different cancers, which may play a role in carcinogenesis, and the MLL3 mutation may influence the alteration of H3K4 methylation. Our studies make it is possible to link genetic changes and epigenetic modifications. Clearly, a large sample cohort study is needed to test H3K4me3 binding patterns in MLL3 mutation patients, as well as in all cancer patients and even normal individuals. Disclosures No relevant conflicts of interest to declare.

Profiling chromatin regulatory landscape: insights into the development of ChIP-seq and ATAC-seq

Chromatin regulatory landscape plays a critical role in many disease processes and embryo development. Epigenome sequencing technologies such as chromatin immunoprecipitation sequencing (ChIP-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) have enabled us to dissect the pan-genomic regulatory landscape of cells and tissues in both time and space dimensions by detecting specific chromatin state and its corresponding transcription factors. Pioneered by the advancement of chromatin immunoprecipitation-chip (ChIP-chip) technology, abundant epigenome profiling technologies have become available such as ChIP-seq, DNase I hypersensitive site sequencing (DNase-seq), ATAC-seq and so on. The advent of single-cell sequencing has revolutionized the next-generation sequencing, applications in single-cell epigenetics are enriched rapidly. Epigenome sequencing technologies have evolved from low-throughput to high-throughput and from bulk sample to the single-cell scope, which unprecedentedly benefits scientists to interpret life from different angles. In this review, after briefly introducing the background knowledge of epigenome biology, we discuss the development of epigenome sequencing technologies, especially ChIP-seq & ATAC-seq and their current applications in scientific research. Finally, we provide insights into future applications and challenges.

INVERSE PROBLEM OF A ONE-DIMENSIONAL MODEL IN MULTILAYER HEAT CONDUCTION

The inverse problem in conducting heat is related to the determination of the boundary condition, rate of heat generation, or thermophysical properties, using temperature measurements at one or more positions of the solid. The inverse problem in conducting heat is mathematically one of the ill-posed problems, because its solution extremely sensitive to measurement errors. For a well-placed problem the following conditions must be satisfied: the solution must exist, it must be unique and must be stable on small changes of the input data. The objective of the work is to estimate the heat flux generated at the tool-chip-chip interface in a manufacturing process. The term "estimation" is used because in the temperature measurements, errors are always present and these affect the accuracy of the calculation of the heat flow.

Về một giải pháp cứng hóa phép tính lũy thừa modulo

Tóm tắt -Nam tính bị giảm cân modulo là nam tính Cạn là một trong những thứ khác nhau. Thời gian thi đấu của bạn là trò chơi, trò chơi, trò chơi, trò chơi, trò chơi điện tử Trọng tâm có thể bị giảm cân. Trong nội bộ của chúng tôi Nam tính chỉ có chế độ tối ưu và thiết kế theo chiều dọc 20 bit bit, chip FPGA XC7z045.trừu tượng- lũy thừa mô đun là hoạt động cơ bản trong thuật toán mã hóa RSA. Đây là một thuật toán phức tạp, tiêu tốn tài nguyên và thời gian để thực hiện (đặc biệt là với số lượng lớn). Phần cứng thực hiện lũy thừa mô-đun trên FPGA sẽ tăng tốc độ, giảm thời gian tính toán theo yêu cầu của thực tiễn. Trung tâm của toán hạng mô đun là phép nhân mô đun số lượng lớn. Trong bài báo này, chúng tôi đã trình bày giới thiệu, phân tích, chọn thuật toán lũy thừa mô đun và phép nhân mô đun Montgomery dựa trên một số nghiên cứu công khai trên thế giới. Hoạt động lũy thừa mô-đun được triển khai với ngôn ngữ phần cứng HDL Verilog với mô-đun được chọn là 2048 bit, chip XC7z045 chip chip.