Genome-wide analysis of the maternal-to-zygotic transition in Drosophila primordial germ cells

Background: During the maternal-to-zygotic transition (MZT) vast changes in the embryonic transcriptome are produced by a combination of two processes: elimination of maternally provided mRNAs and synthesis of new transcripts from the zygotic genome. Previous genome-wide analyses of the MZT have been restricted to whole embryos. Here we report the first such analysis for primordial germ cells (PGCs), the progenitors of the germ-line stem cells. Results: We purified PGCs from Drosophila embryos, defined their proteome and transcriptome, and assessed the content, scale and dynamics of their MZT. Transcripts encoding proteins that implement particular types of biological functions group into nine distinct expression profiles, reflecting coordinate control at the transcriptional and posttranscriptional levels. mRNAs encoding germ-plasm components and cell-cell signaling molecules are rapidly degraded while new transcription produces mRNAs encoding the core transcriptional and protein synthetic machineries. The RNA-binding protein Smaug is essential for the PGC MZT, clearing transcripts encoding proteins that regulate stem cell behavior, transcriptional and posttranscriptional processes. Computational analyses suggest that Smaug and AU-rich element binding proteins function independently to control transcript elimination. Conclusions: The scale of the MZT is similar in the soma and PGCs. However, the timing and content of their MZTs differ, reflecting the distinct developmental imperatives of these cell types. The PGC MZT is delayed relative to that in the soma, likely because relief of PGC-specific transcriptional silencing is required for zygotic genome activation as well as for efficient maternal transcript clearance.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000305391700004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biotechnology & Applied MicrobiologyGenetics & HereditySCI(E)20ARTICLE2null1

Fetal lung underdevelopment is rescued by administration of amniotic fluid stem cell extracellular vesicles in rodents

Fetal lung underdevelopment, also known as pulmonary hypoplasia, is characterized by decreased lung growth and maturation. The most common birth defect found in babies with pulmonary hypoplasia is congenital diaphragmatic hernia (CDH). Despite research and clinical advances, CDH babies still have high morbidity and mortality rates, which are directly related to the severity of lung underdevelopment. To date, there is no effective treatment that promotes fetal lung growth and maturation. Herein, we describe a stem cell-based approach that enhances fetal lung development via the administration of extracellular vesicles (EVs) derived from amniotic fluid stem cells (AFSCs). Using fetal rodent models of pulmonary hypoplasia (primary epithelial cells, organoids, explants, and in vivo), we demonstrated that AFSC-EV administration promotes branching morphogenesis and alveolarization, rescues tissue homeostasis, and stimulates epithelial cell and fibroblast differentiation. We confirmed this regenerative ability in human models of lung injury, where human AFSC-EVs obtained following good manufacturing practices restored pulmonary epithelial homeostasis. Investigating EV mechanism of action by tracking AFSC-EV cargo transfer, profiling EV protein and RNA content, and sequencing target lung epithelial cells, we found that AFSC-EV beneficial effects were exerted via the release of RNA cargo. Particularly, miRNAs that regulate the expression of genes involved in lung development, such as the miR17~92 cluster and its paralogues, were highly enriched in AFSCEVs and were increased in AFSC-EV-treated primary lung epithelial cells compared to untreated cells. Our findings suggest that AFSC-EVs hold regenerative ability for underdeveloped fetal lungs, demonstrating potential for therapeutic application in patients with pulmonary hypoplasia

Ueber die Wasserstoffionenkonzentration an den Sekreten und Schleimhauten bei Nasen-Kieferhohlen- und Rachenerkrankungen

Auf dem Oto-Rhino-und Laryngologischen Gebiet sind bisher physikalisch-chemische Untersuchungen sehr wenig erforscht worden, besonders liegen hier nur sparliche Studien uber das Verhalten der Wasserstoffionenkonzentration vor. Ich habe mit Hilfe der Chinhydronelektrode das PH in den Sekreten bei Rhinitis chronica, Sinuitis maxillaris chronica gemessen, sowie an den Hohlenschleimhauten bei Sinuitis maxillaris chronica, gleichfalls in den Gewebssaften bei Gaumen- und Rachen-tonsillitiden bestimmt. Aus den erhaltenen PH-Werten in Zusammenhang mit dem Krankheitsverlauf lassen sich folgende Schlusse ziehen: 1. PH-Werte: In Nasensekreten bei Rhinitis Katarrhalis chronica 7.68-8.10, wahrend als normales PH bei Gesunden 8.10-8.33 festgestellt wurde. An den Krusten bei Rhinitis atrophicans chronica betrug das PH 6.79-7.35, dagegen an den unterhalb der Krusten sich befindlichen weichen Sekreten PH 7.52-8.0.2. 2. Die Staungssekrete bei Sinuitis maxillaris chronica zeigten ein PH 6.19-8.09. In rein eitrigen Sekreten bei eitriger Form der Erkrankung fand eine Verschiebung nach der sauren, in den schleimigen bei katarrhalischer Form nach der alkalischen Seite hin statt, und bei den ersteren befanden sich die Eiterzellen in hochgradigen Regressionszu-standen, welche Prozesse bei den letzteren verhaltnissmassig geringfugig waren. An den klar gelblichen, flussigen Sekreten bei Zysten und Hydrops bekam man PH=7.39-7.45, ein Alkalitatsgrad, welcher dem PH des Blutes bei normalen Menschen entspricht. Es ist also anzunehmen, dass der PH-Wert der Sekrete das Ergebnis der Mischung der einzelnen Komponenten der Absonderung (Eiter, Schleim, Exsudat) ist und gleichzeitig von der Starke der regressiven Degeneration der Eiterzellen abhangt. 3. Mit der Erleichterung der Symptome durch geeignete Hohlenspulung bei Sinuitis maxillaris chronica gehen die regressiven Prozesse an den Eiterzellen auch zuruck, steigen die PH-Werte bis etwas 8.0 an, dann pflegt das Leiden allmahich zur Heilung zu kommen. Die PH-Betrage und die Starke der regressive

From DNA Topology to Pubertal Onset: Using Integrative Genomic Approaches to Study Transcriptional Regulation

Studying how cellular transcriptional programs are precisely controlled is essential for understanding development and disease. In this thesis, I first explore an essential aspect of transcriptional control: DNA topology. Topoisomerase II (TOP2) proteins regulate DNA topology by creating transient double-strand breaks. Topoisomerase II beta (TOP2B) facilitates gene transcription and is essential for postnatal development. However, the genome biology of TOP2B remains largely unknown. Through integrative analyses of the genome-wide binding profiles of TOP2B and many other transcriptional regulators, I discover that TOP2B associates with DNase I hypersensitive sites, tissue-specific TF binding, and evolutionarily conserved enhancers in the mouse genome. Particularly, TOP2B coincides with CTCF and cohesin, with a structural ordering at topologically associating domain (TAD) boundaries. I conclude that TOP2B is positioned to solve topological problems at critical cis-regulatory regions and its highly ordered binding is a prevalent feature of CTCF/cohesin sites flanking TAD boundaries. Next, we applied three gene expression profiling methods and integrative bioinformatics approaches to study the expression of genes associated with pubertal onset. Timing of pubertal onset varies in the general population and is associated with diverse later-life health outcomes. Studies of pubertal disorders and genome-wide association studies (GWAS) have identified hundreds of puberty-associated genes. However, their specific functions are not well characterized. To address this problem, I first showed that the expression of these puberty-associated genes is enhanced in multiple neuronal tissues using a human transcriptome dataset. We then used a sensitive qPCR platform to profile the mouse orthologs of these selected genes (n=179) in several mouse tissues during postnatal development in both sexes. To expand beyond the selected genes, we developed an automated 3’UTR-seq method to characterize changes of the transcriptome during postnatal development in mouse pituitary samples. My analyses have revealed abundant tissue-, age-, and sex-specific expression patterns of puberty-associated genes. These findings not only inform future functional studies but also provide valuable insights into the transcriptional regulation of the onset of puberty. Focusing on two distinct biological problems, my thesis explores the usage of integrative genomic approaches in studying transcriptional regulation.Ph.D

A New Explanation for the Effect of Dynamic Strain Aging on Negative Strain Rate Sensitivity in Fe–30Mn–9Al–1C Steel

In this study, the evolution of the mechanical properties of Fe–30Mn–9Al–1C steel has been determined in tensile tests at strain rates of 10−4 to 102 s−1. The results show that the strain rate sensitivity becomes a negative value when the strain rate exceeds 100 s−1 and this abnormal evolution is attributed to the occurrence of dynamic strain aging. Due to the presence of intergranular κ-carbides, the fracture modes of steel include ductile fracture and intergranular fracture. The values of dislocation arrangement parameter M were obtained using a modified Williamson–Hall plot. It has been found that once the strain rate sensitivity becomes negative, the interaction of dislocations in the steel is weakened and the free movement of dislocation is enhanced. Adiabatic heating promotes the dynamic recovery of steel at a high strain rate

Correlation of Stacking Fault Energy with Deformation Mechanism in Cu-(2, 20)Zn Alloys

Copper-zinc alloys with different zinc contents contain different stacking fault energies (SFE). The influence of SFE on the deformation mechanism during surface mechanical attrition treatment was studied in this work. Research results indicate that the deformation mechanism directly correlated with the SFE in Cu-Zn alloys. Deformation twinning plays a paramount role during original deformation in Cu-20Zn (19 mJ/m2). However, for Cu-2Zn alloy with low-medium SFE (38 mJ/m2), the deformation mechanism is dominated by the dislocation slipping. Microbands are the predominant microstructural features in large strain and high strain rate regions for both Cu-Zn alloys in the present study. They are likely to be formed by the splitting of the high-density dislocation walls

Corrosion Behavior of the As-Cast and As-Solid Solution Mg-Al-Ge Alloy

The corrosion behavior of Mg-3Al-xGe (x = 1, 3, 5) alloy in as-cast and as-solid was investigated by virtue of microstructure, corrosion morphology observation, and electrochemical measurement. Among the as-cast alloys, the corrosion rate of Mg-3Al-1Ge with a discontinuous bar-morphology was the highest, which was 101.7 mm·a−1; the corrosion rate of Mg-3Al-3Ge with a continuous network distribution was the lowest, which was 23.1 mm·a−1; and the corrosion rate of Mg-3Al-5Ge of Ge-enriched phase with sporadic distribution was in-between, which was 63.9 mm·a−1. It is suggested that the morphology of the Mg2Ge phase changes with a change in Ge content, which affects the corrosion performance of the alloy. After solid solution treatment, the corrosion rate of the corresponding solid solution alloy increased—Mg-3Al-1Ge to 140.5 mm·a−1, Mg-3Al-3Ge to 52.9 mm·a−1, and Mg-3Al-5Ge to 87.3 mm·a−1, respectively. After investigation of the microstructure, it can be suggested that solid solution treatment dissolves the Mg17Al12 phase, which changes the phase composition of the alloy and also affects its microstructure, thus affecting its corrosion performance

The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice.

During gestation, uterine smooth muscle cells transition from a state of quiescence to one of contractility, but the molecular mechanisms underlying this transition at a genomic level are not well-known. To better understand these events, we evaluated the epigenetic landscape of the mouse myometrium during the pregnant, laboring, and postpartum stages. We generated gestational time point-specific enrichment profiles for histone H3 acetylation on lysine residue 27 (H3K27ac), histone H3 trimethylation of lysine residue 4 (H3K4me3), and RNA polymerase II (RNAPII) occupancy by chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq), as well as gene expression profiles by total RNA-sequencing (RNA-seq). Our findings reveal that 533 genes, including known contractility-driving genes (Gap junction alpha 1 [Gja1], FBJ osteosarcoma oncogene [Fos], Fos-like antigen 2 [Fosl2], Oxytocin receptor [Oxtr], and Prostaglandin G/H synthase 2 (Ptgs2), for example), are up-regulated at day 19 during active labor because of an increase in transcription at gene bodies. Labor-associated promoters and putative intergenic enhancers, however, are epigenetically activated as early as day 15, by which point the majority of genome-wide H3K27ac or H3K4me3 peaks present in term laboring tissue is already established. Despite this early exhibited histone signature, increased noncoding enhancer RNA (eRNA) production at putative intergenic enhancers and recruitment of RNAPII to the gene bodies of labor-associated loci were detected only during labor. Our findings indicate that epigenetic activation of the myometrial genome precedes active labor by at least 4 days in the mouse model, suggesting that the myometrium is poised for rapid activation of contraction-associated genes in order to exit the state of quiescence