scholarly journals Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators

2019 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Nyssa Adams ◽  
San-pin Wu ◽  
Steven L. Young ◽  
...  

ABSTRACTContextPoor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility.ObjectiveTo define PGR-regulated molecular mechanisms and epithelial roles in receptivity.DesignRNA-seq and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the WOI in endometrium of fertile women.SettingEndometrial biopsies from the proliferative and mid-secretory phases were analyzed.Patients or Other ParticipantsParticipants were fertile, reproductive aged (18-37) women with normal cycle length; and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study.InterventionsThere were no interventions during this study.Main Outcome MeasuresHere we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle-dependently to regulate genes involved in uterine cell differentiation and function.Results653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, EMT, cell death, interleukin/STAT signaling, estrogen response, and MTORC1 response. Transcriptome of the epithelium identified 3,052 DEGs, of which 658 were uniquely regulated. Transcription factors IRF8 and MEF2C were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized.ConclusionPGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.PrécisUsing a combination of RNA-seq and PGR ChIP-seq, novel signaling pathways and epithelial regulators were identified in the endometrium of fertile women during the window of implantation.

2019 ◽  
Vol 105 (4) ◽  
pp. e1419-e1439 ◽  
Author(s):  
Ru-pin Alicia Chi ◽  
Tianyuan Wang ◽  
Nyssa Adams ◽  
San-pin Wu ◽  
Steven L Young ◽  
...  

Abstract Context Poor uterine receptivity is one major factor leading to pregnancy loss and infertility. Understanding the molecular events governing successful implantation is hence critical in combating infertility. Objective To define Progesterone Receptor (PGR)-regulated molecular mechanisms and epithelial roles in receptivity. Design RNA-sequencing and PGR-ChIP-seq were conducted in parallel to identify PGR-regulated pathways during the Window of implantation (WOI) in endometrium of fertile women. Setting Endometrial biopsies from the proliferative and mid-secretory phases were analyzed. Patients or Other Participants Participants were fertile, reproductive aged (18–37 years) women with normal cycle length, and without any history of dysmenorrhea, infertility, or irregular cycles. In total, 42 endometrial biopsies obtained from 42 women were analyzed in this study. Interventions There were no interventions during this study. Main Outcome Measures Here we measured the alterations in gene expression and PGR occupancy in the genome during the WOI, based on the hypothesis that PGR binds uterine chromatin cycle dependently to regulate genes involved in uterine cell differentiation and function. Results 653 genes were identified with regulated PGR binding and differential expression during the WOI. These were involved in regulating inflammatory response, xenobiotic metabolism, epithelial mesenchymal transition, cell death, interleukin/Signal Transducer And Activator Of Transcription (STAT) signaling, estrogen response, and Mammalian target of rapamycin complex 1 (MTORC1) response. Transcriptome of the epithelium identified 3052 differentially expressed genes, of which 658 were uniquely regulated. Transcription factors Interferon Regulatory Factor 8 (IRF8) and Myocyte Enhancer Factor 2C (MEF2C) were found to be regulated in the epithelium during the WOI at the protein level, suggesting potentially important functions that are previously unrecognized. Conclusion PGR binds the genomic regions of genes regulating critical processes in uterine receptivity and function.


2021 ◽  
Author(s):  
Marco Tulio Solano De la Cruz ◽  
Esteban Elías Escobar Hernández ◽  
Jorge Arturo Arciniega González ◽  
Rocío Del Pilar Rueda Zozaya ◽  
Mauricio Luna Rodríguez ◽  
...  

Background: F. oxysporum as a species complex (FOSC) possess the capacity, to specialize into host-specific pathogens deriving into formae speciales. This with the help of horizontal gene transfer (HGT) between pathogenic and endophytic individuals of FOSC. From these pathogenic forma speciales, F. oxysporum f. sp. vanillae (Fov) is the causal agent of fusarium wilt producing root and stem rot (RSR) positions itself was the main phytosanitary problem in vanilla plantations worldwide. Nonetheless, the origin of this forma specialis and the behavioral genetics dictating the endophytic/pathogenic Fusarium lifestyles are still unknown. To elucidate the underlying molecular mechanisms that establish these behaviors we analyzed the RNA-seq libraries of two-times frames of vanilla-fov interactions. Results: Our analyses identified the sets of transcripts corresponding to Fov pathogenic strain JAGH3 during the two-times frames of the infection as the sets of the transcripts belonging to endophytic Fox in vanilla. Functional predictions of de novo annotated transcripts as the enriched GO terms with the overrepresented metabolic pathways associated to them allowed us to identify the molecular processes that establish the pathogenic lifestyle in Fov being virulence, hypervirulence, sporulation, conidiation, necrosis and fusaric acid related genes with the carbohydrates, amino acids and proteins, glycerophospholipids and autophagy metabolic pathways that are key regulators of spores germination and pathogenicity establishment as the underlying mechanisms behind this behavior. As the absence of these were found in the vanilla endophytic Fox. Conclusions: This work reveals the main players of the behavioral genetics in pathogenic Fov/endophytic Fox in V. planifolia Jacks. Its pathogenic strategy allows Fov to infect in a SIX genes-independent manner. As the other pathogenic elements found in this study could be explained by the presence of pathogenicity islands and genomic regions associated with supernumerary chromosomes in Fov. These play a central role as carriers of genes involved with pathogenic activity and can be obtained through HGT.


2019 ◽  
Author(s):  
Hajime Ohyanagi ◽  
Kosuke Goto ◽  
Sónia Negrão ◽  
Rod A. Wing ◽  
Mark A. Tester ◽  
...  

AbstractDomestication is anthropogenic evolution that fulfills mankind’s critical food demand. As such, elucidating the molecular mechanisms behind this process promotes the development of future new food resources including crops. With the aim of understanding the long-term domestication process of Asian rice and by employing the Oryza sativa subspecies (indica and japonica) as an Asian rice domestication model, we scrutinized past genomic introgressions between them as traces of domestication. Here we show the genome-wide introgressive region (IR) map of Asian rice, by utilizing 4,587 accession genotypes with a stable outgroup species, particularly at the finest resolution through a machine learning-aided method. The IR map revealed that 14.2% of the rice genome consists of IRs, including both wide IRs (recent) and narrow IRs (ancient). This introgressive landscape with their time calibration indicates that introgression events happened in multiple genomic regions over multiple periods. From the correspondence between our wide IRs and the so-called selective sweep regions, we provide a definitive answer to a long-standing controversy over the evolutionary origin of Asian rice domestication, single or multiple origins: It heavily depends upon which regions you pay attention to, implying that wider genomic regions represent immediate short history of Asian rice domestication as a likely support to the single origin, while its ancient history is interspersed in narrower traces throughout the genome as a possible support to the multiple origin.


2021 ◽  
Vol 9 (10) ◽  
pp. 2081
Author(s):  
Áurea Martins Gabriel ◽  
Adan Galué-Parra ◽  
Washington Luiz Assunção Pereira ◽  
Ketil Winther Pedersen ◽  
Edilene Oliveira da Silva

Leishmania parasites are a group of kinetoplastid pathogens that cause a variety of clinical disorders while maintaining cell communication by secreting extracellular vesicles. Emerging technologies have been adapted for the study of Leishmania-host cell interactions, to enable the broad-scale analysis of the extracellular vesicles of this parasite. Leishmania extracellular vesicles (LEVs) are spheroidal nanoparticles of polydispersed suspensions surrounded by a layer of lipid membrane. Although LEVs have attracted increasing attention from researchers, many aspects of their biology remain unclear, including their bioavailability and function in the complex molecular mechanisms of pathogenesis. Given the importance of LEVs in the parasite-host interaction, and in the parasite-parasite relationships that have emerged during the evolutionary history of these organisms, the present review provides an overview of the available data on Leishmania, and formulates guidelines for LEV research. We conclude by reporting direct methods for the isolation of specific LEVs from the culture supernatant of the promastigotes and amastigotes that are suitable for a range of different downstream applications, which increases the compatibility and reproducibility of the approach for the establishment of optimal and comparable isolation conditions and the complete characterization of the LEV, as well as the critical immunomodulatory events triggered by this important group of parasites.


2020 ◽  
Author(s):  
Federico Miozzo ◽  
Luca Stickely ◽  
Damla Tas ◽  
Nicolas Loncle ◽  
Irina Nikonenko ◽  
...  

ABSTRACTThe degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson’s Disease (PD). Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. We further show that conditional ablation of Nato3, a mouse homolog of Fer2, in differentiated DA neurons results in locomotor impairments and mitochondrial abnormality in aged mice. Our results reveal the essential and conserved role of Fer2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modelling and treating PD.


Metahumaniora ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 54
Author(s):  
Erlina Zulkifli Mahmud ◽  
Taufik Ampera ◽  
Yuyu Yohana Risagarniwa ◽  
Inu Isnaeni Sidiq

Kedudukan dan fungsi bahasa sebagai alat komunikasi manusia mencakup seluruh bidang kehidupan termasuk ilmu pengetahuan antara lain terkait sejarah peradaban manusia; bagaimana manusia mempertahankan hidupnya, bagaimana manusia memperlakukan alam, bagaimana alam menyediakan segala kebutuhan manusia. Apa yang dilakukan manusia saat ini, saat lampau, dan apa yang dilakukan manusia jauh di masa prasejarah, bagaimana kondisi alam di masa-masa tersebut, apa perubahan dan perkembangannya, dapat didokumentasikan melalui bahasa, divisualisasikan kembali, lalu dipajang sebagai salah satu upaya konversai dan preservasi dalam satu institusi yang disebut museum. Penelitian ini membahas kedudukan dan fungsi bahasa dalam permuseuman. Bagaimana kedudukan dan fungsi bahasa dalam permuseuman baik dalam informasi yang disampaikan oleh pemandu wisata museumnya maupun yang terpajang menyertai benda-benda dan gambar-gambar merupakan tujuan dari penelitian ini. Metode penelitian yang digunakan adalah gabungan antara metode lapangan dan metode literatur. Hasil penelitian menunjukkan bahwa secara umum kedudukan bahasa Indonesia berada pada urutan pertama setelah Bahasa Inggris dan keberadaan kedua bahasa dalam permuseuman ini melibatkan dua fungsi utama bahasa, yakni fungsi komunikatif dan fungsi informatif.The existence and function of language  as a medium of communication covers all fields of human life including knowledge, one of them is the history of human civilization; how humans survived, how human utilized nature for their lives, and how nature provides all the necessities for humans. What humans have been doing now, what they have done in the past and far before that in the pre-history time, how the conditions of the nature at those times were and what changes as well as progresses occurred are documented using language, then re-visualized,  displayed as one of conservation and preservation acts in an institution called museum. This research discusess the existence and function of language in museums. How important the existence of a language in museums and what language functions used in museums both in informations given by the museum guides and on the displays accompanying objects and pictures are the aims of this research. The methods used are the combination between field research and library research. The results show that generally the existence of Indonesian language plays more important role than English and both languages have two main functions; communicative function and informative function.     


2018 ◽  
Author(s):  
Stacy A. Malaker ◽  
Kayvon Pedram ◽  
Michael J. Ferracane ◽  
Elliot C. Woods ◽  
Jessica Kramer ◽  
...  

<div> <div> <div> <p>Mucins are a class of highly O-glycosylated proteins that are ubiquitously expressed on cellular surfaces and are important for human health, especially in the context of carcinomas. However, the molecular mechanisms by which aberrant mucin structures lead to tumor progression and immune evasion have been slow to come to light, in part because methods for selective mucin degradation are lacking. Here we employ high resolution mass spectrometry, polymer synthesis, and computational peptide docking to demonstrate that a bacterial protease, called StcE, cleaves mucin domains by recognizing a discrete peptide-, glycan-, and secondary structure- based motif. We exploited StcE’s unique properties to map glycosylation sites and structures of purified and recombinant human mucins by mass spectrometry. As well, we found that StcE will digest cancer-associated mucins from cultured cells and from ovarian cancer patient-derived ascites fluid. Finally, using StcE we discovered that Siglec-7, a glyco-immune checkpoint receptor, specifically binds sialomucins as biological ligands, whereas the related Siglec-9 receptor does not. Mucin-specific proteolysis, as exemplified by StcE, is therefore a powerful tool for the study of glycoprotein structure and function and for deorphanizing mucin-binding receptors. </p> </div> </div> </div>


Author(s):  
Benjamin E. Reynolds

The central place of revelation in the Gospel of John and the Gospel’s revelatory telling of the life of Jesus are distinctive features of John when compared with the Synoptic Gospels; yet, when John is compared among the apocalypses, these same features indicate John’s striking affinity with the genre of apocalypse. By paying attention to modern genre theory and making an extensive comparison with the standard definition of “apocalypse,” the Gospel of John reflects similarities with Jewish apocalypses in form, content, and function. Even though the Gospel of John reflects similarities with the genre of apocalypse, John is not an apocalypse, but in genre theory terms, John may be described as a gospel in kind and an apocalypse in mode. John’s narrative of Jesus’s life has been qualified and shaped by the genre of apocalypse, such that it may be called an “apocalyptic” gospel. Understanding the Fourth Gospel as “apocalyptic” Gospel provides an explanation for John’s appeal to Israel’s Scriptures and Mosaic authority. Possible historical reasons for the revelatory narration of Jesus’s life in the Gospel of John may be explained by the Gospel’s relationship with the book of Revelation and the history of reception concerning their writing. An examination of Byzantine iconographic traditions highlights how reception history may offer a possible explanation for reading John as “apocalyptic” Gospel.


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